Nicotinic receptor-mediated reduction in l-DOPA-induced dyskinesias may occur via desensitization
Open accessAbstract
L-DOPA-induced dyskinesias in Parkinson's disease are a significant clinical problem for which few therapies are available. We recently showed that nicotine reduces L-DOPA-induced abnormal involuntary movements (AIMs) in parkinsonian animals, suggesting it may be useful for the treatment of L-DOPA-induced dyskinesias. The present experiments were performed to understand the mechanisms whereby nicotine reduces L-DOPA-induced AIMs. We used a well established model of dyskinesias, L-DOPA-treated unilateral 6-hydroxydopamine-lesioned rats. Dose-ranging studies showed that injection of 0.1 mg/kg nicotine once or twice daily for 4 or 10 days most effectively reduced AIMs, with no worsening of parkinsonism. Importantly, a single nicotine injection did not reduce AIMs, indicating that nicotine's effect is caused by long-term rather than short-term molecular changes. Administration of the metabolite cotinine did not reduce AIMs, suggesting a direct effect of nicotine. Experiments with the nicotinic receptor (nAChR) antagonist mecamylamine were done to determine whether nicotine acted via a receptor-mediated mechanism. Unexpectedly, several days of mecamylamine injection (1.0 mg/kg) alone significantly ameliorated dyskinesias to a comparable extent as nicotine. The decline in AIMs with combined nicotine and mecamylamine treatment was not additive, suggesting that nicotine exerts its effects via a nAChR interaction. This latter finding, combined with data showing that mecamylamine reduced AIMs to a similar extent as nicotine, and that nicotine or mecamylamine treatment both decreased alpha6beta2* and increased alpha4beta2* nAChR expression, suggests that the nicotine-mediated improvement in L-DOPA-induced AIMs may involve a desensitization block. These data have important implications for the treatment of L-DOPA-induced dyskinesias in Parkinson's disease.
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TL;DR
In 6-OHDA-lesioned, L-DOPA-treated rats, repeated nicotine or mecamylamine reduced L-DOPA-induced abnormal involuntary movements (AIMs), whereas acute nicotine and cotinine did not. The similar effects of nicotine and mecamylamine, their non-additivity when combined, and parallel changes in α6β2* and α4β2* nAChRs suggest nicotine may act via nAChR desensitization/block.
Key findings
- Nicotine dose-response: 0.1 mg/kg once daily for 4 days maximally reduced total, orolingual, and forelimb AIMs; 0.01 and 0.05 mg/kg had no significant effect, and higher doses (0.25–0.75 mg/kg) also reduced AIMs but less pronouncedly. A single nicotine injection did not reduce AIMs; multiple-day dosing was required, with twice-daily 4-day treatment producing somewhat greater reduction and 10-day once-daily treatment no further reduction. Nicotine did not worsen parkinsonism: forelimb use asymmetry was unaffected, and L-DOPA-induced contralateral rotations were similar with saline (677 ± 230, n = 10) and nicotine (675 ± 166, n = 9).
- Cotinine did not reduce AIMs: minipump cotinine at 2.5 or 5 mg/kg/day for 3 weeks had no effect on total, axial, orolingual, or forelimb AIMs despite plasma cotinine levels of 353 ± 126 and 1202 ± 61 ng/ml, respectively. Nicotine injection at 0.1 mg/kg yielded plasma cotinine of 202 ± 26 ng/ml, and minipump nicotine at 0.5 mg/kg/day yielded 115 ± 25 ng/ml, both associated with reduced AIMs.
- Mecamylamine alone reduced AIMs: acute 2 mg/kg had no significant effect, but 4 days of 1.0 mg/kg significantly reduced total (p < 0.05), orolingual (p < 0.01), and forelimb (p < 0.05) AIMs, with a trend for axial AIMs. Combined 4-day nicotine (0.1 mg/kg) plus mecamylamine (1.0 mg/kg) was not additive and was similar to either drug alone.
- Receptor binding: nicotine (0.2 mg/kg) or mecamylamine (1 mg/kg) daily for 14 days both significantly decreased striatal [125I]α-CtxMII/α6β2* binding and increased [125I]epibatidine/α4β2* binding on the unlesioned, but not lesioned, side (p < 0.01). The lesioned striatum showed a 99% decline in dopamine transporter binding (0.9 ± 0.2% of control).
Methods
- Male Sprague-Dawley rats were unilaterally lesioned with 6-OHDA into the right medial forebrain bundle; rats turning more than four complete turns/minute after amphetamine were used. They received daily L-DOPA methyl ester (8 mg/kg) plus benserazide (15 mg/kg) s.c., and AIMs were scored for axial, orolingual, and forelimb components on a 0–4 scale over 3 h (maximum possible score 108).
- Behavioral experiments used one set of 20 rats; drugs included nicotine (0.01–0.75 mg/kg injection; 0.1–2 mg/kg/day minipump), cotinine (2.5 or 5 mg/kg/day minipump), and mecamylamine (0.5–2 mg/kg), with ≥3-day washouts. Limb use asymmetry and L-DOPA-induced contralateral rotations assessed motor function; plasma cotinine was measured by EIA.
- Binding studies used a separate set of 6-OHDA-lesioned rats treated daily for 14 days with nicotine (0.2 mg/kg) or mecamylamine (1 mg/kg); autoradiography measured α6β2* ([125I]α-CtxMII), α4β2* ([125I]epibatidine plus cold α-CtxMII), and dopamine transporter ([125I]RTI-121). Statistics used one-way ANOVA with Dunnett’s test, repeated-measures ANOVA with Bonferroni post hoc, and p < 0.05 as significant.
Limitations
- Stated: the mechanisms whereby nAChR-mediated desensitization decreases L-DOPA-induced AIMs remain to be investigated, and the nAChR subtypes responsible have not yet been elucidated. The lack of cotinine effect may be due to insufficient brain entry or to the mode of administration, and final efficacy requires a clinical trial.
- Stated: L-DOPA-induced AIMs may be influenced by previous dosing of agonists and antagonists, although repeat experiments with the same doses yielded similar declines.
- Evident from the text: findings are limited to unilateral 6-OHDA-lesioned rats, with no human data; desensitization is inferred rather than directly measured; receptor changes were measured in separate animals and only on the unlesioned side; behavioral data were pooled from one or two experiments with n = 9–10 per group.
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- Findingown data
Saline-treated control rats had stable total L-DOPA-induced AIM scores across treatment regimes, with a mean of 69.1 ± 3.2.
“Values for the saline-treated control rats remained stable over the different treatment regimes with a mean total L-DOPA-in- duced AIM score of 69.1 Ϯ 3.2 (n ϭ 54, which represent the scores from nine rats over six separate experiments).”
Quote in the paperSubstantial claim - Findingown data
Plasma cotinine levels 3 to 4 hours after a 0.1 mg/kg nicotine injection were 202 ± 26 ng/ml.
“Measurement of plasma cotinine levels (Table 1) 3 to 4 h after injection of the 0.1 mg/kg nicotine dose yielded concentrations of 202 Ϯ 26 ng/ml (n ϭ 10).”
Quote in the paperSubstantial claim - Findingown data
Three weeks of cotinine treatment at 2.5 or 5 mg/kg/day had no effect on total, axial, orolingual, or forelimb AIMs despite high plasma cotinine levels.
“The results in Table 2 show that, despite high plasma cotinine levels, 3 weeks of cotinine treatment had no effect on total, axial, orolingual, or forelimb AIMs.”
Quote in the paperSubstantial claim - Findingown data
Nicotine at 0.01 and 0.05 mg/kg had no significant effect on L-DOPA-induced AIMs.
“The results in Fig. 1 show that nicotine (0.01 and 0.05 mg/kg) treatments had no significant effect on L-DOPA-induced AIMs.”
Quote in the paperSubstantial claim - Findingown data
Higher nicotine doses were associated with anxiety-like behaviors such as irritability and nervousness.
“It should be noted that the higher doses were also associated with the development of anxietylike behaviors such as irritability and nervousness.”
Quote in the paperNot a substantial claim
- Findingown data
Four days of nicotine at 0.1 mg/kg did not affect parkinsonism either on or off L-DOPA.
“The results show that 4 days of nicotine (0.1 mg/kg) treatment did not affect parkinsonism either on or off L-DOPA.”
Quote in the paperSubstantial claim - Findingown data
The dose-response curve pattern for minipump nicotine was very similar to that observed with injection.
“The pattern of the dose-response curve was very similar to that observed when nicotine was given via injection (see Fig. 1).”
Quote in the paperSubstantial claim - Findingown data
Higher nicotine doses showed a trend for a decrease in axial AIMs.
“By contrast, significant declines in total, orolingual, and forelimb AIMs were observed with the higher nicotine doses (0.5, 1.0, and 2.0 mg/kg/day), with a trend for a decrease in axial AIMs.”
Quote in the paperNot a substantial claim - Findingown data
A single 2 mg/kg dose of mecamylamine had no significant effect on AIMs.
“The results in Fig. 5 show that a single (short-term) dose of mecamylamine (2 mg/kg) given 30 min before L-DOPA had no significant effect on AIMs.”
Quote in the paperSubstantial claim - Findingown data
Plasma cotinine levels at the nicotine dose (0.5 mg/kg/day) that produced maximal reduction in L-DOPA-induced AIMs were 115 ± 25 ng/ml (n=10).
“Plasma cotinine levels at the dose of nicotine (0.5 mg/kg/ day) that resulted in a maximal reduction in L-DOPA-in- duced AIMs were 115 Ϯ 25 ng/ml (n ϭ 10) (Table 1).”
Quote in the paperSubstantial claim - Findingcitation
Once-daily nicotine for 4 days significantly reduced total, oral, and forelimb AIMs.
“However, as previously shown, oncedaily nicotine injection for 4 days significantly (p Ͻ 0.01) reduced total, oral, and forelimb AIMs.”
Quote in the paperSubstantial claim - Findingown data
Higher nicotine doses (0.5, 1.0, and 2.0 mg/kg/day) significantly reduced total, orolingual, and forelimb AIMs.
“By contrast, significant declines in total, orolingual, and forelimb AIMs were observed with the higher nicotine doses (0.5, 1.0, and 2.0 mg/kg/day), with a trend for a decrease in axial AIMs.”
Quote in the paperSubstantial claim - Findingown data
Twice-daily nicotine for 4 days produced a somewhat greater reduction in total, orolingual, and forelimb AIMs than once-daily dosing.
“We also tested twice-daily nicotine injection for 4 days; this treatment resulted in a somewhat greater reduction in total, orolingual, and forelimb AIMs compared with once-daily injection.”
Quote in the paperNot a substantial claim - Findingcitation
Nicotine reduces L-DOPA-induced AIMs similarly whether given intermittently via injection or drinking water or constantly via minipump implantation.
“Further support for a role for desensitization stems from our experiments showing a similar reduction in L-DOPA- induced AIMs whether nicotine was given intermittently via injection or drinking water (Bordia et al., 2008) or constantly via minipump implantation.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bordia et al., 2008 source
Not checked in the free run.
- Rests on an assumption: Minipump administration results in a slow continual release of nicotine that readily promotes receptor desensitization.
- Findingown data
Both nicotine and mecamylamine treatment led to a significant decrease in striatal α6β2* nAChR binding sites on the unlesioned side, but not the lesioned side, compared with vehicle-treated rats.
“Both nicotine and mecamylamine treatment led to a significant decrease (p Ͻ 0.01) in striatal [ 125 I]␣-CtxMII or ␣62* nAChR binding sites on the unlesioned, but not lesioned, side when compared with vehicle-treated rats.”
- Also stated in: § Discussion · plain
“These showed that nicotine or mecamylamine both resulted in declines in ␣62* nAChRs in the unlesioned, but not lesioned, striatum.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
Control rats had a stable mean total L-DOPA-induced AIMs score of 62.6 ± 3.8 (n=27; nine rats over three experiments).
“The values for the controls remained stable with a mean total L-DOPA-induced AIMs score of 62.6 Ϯ 3.8 (n ϭ 27; which represent the scores from nine rats over three separate experiments).”
Quote in the paperNot a substantial claim - Findingown data
A single nicotine injection did not reduce L-DOPA-induced AIMs.
“The results in Fig. 3 show that a single (short-term) injection of nicotine did not attenuate L-DOPA-induced AIMs.”
- Also stated in: § Abstract · hedged
“Importantly, a single nicotine injection did not reduce AIMs, indicating that nicotine's effect is caused by long-term rather than short-term molecular changes.”
Quote in the paperSubstantial claim - Also stated in: § Abstract · hedged
- Findingown data
Extending nicotine treatment to 10 days did not further reduce AIMs.
“No further reduction in AIMs was obtained by increasing the length of nicotine treatment time (10 days).”
Quote in the paperSubstantial claim - Findingown data
Acute nicotine exposure did not reduce L-DOPA-induced AIMs.
“The results show that a single (short-term) injection of nicotine administered 10 min before L-DOPA did not diminish L-DOPA-induced AIMs.”
Quote in the paperSubstantial claim - Findingown data
Four days of once-daily mecamylamine significantly attenuated L-DOPA-induced AIMs.
“However, 4 days of once-daily injection of varying doses of mecamylamine significantly attenuated L-DOPA-induced AIMs.”
Quote in the paperSubstantial claim - Findingown data
Several days of mecamylamine injection at 1.0 mg/kg alone significantly ameliorated dyskinesias to an extent comparable to nicotine.
“Unexpectedly, several days of mecamylamine injection (1.0 mg/kg) alone significantly ameliorated dyskinesias to a comparable extent as nicotine.”
Quote in the paperSubstantial claim - Findingown data
L-DOPA-induced contralateral turning was similar in saline- and nicotine-treated rats.
“Contralateral turning was similar in rats receiving saline (677 Ϯ 230, n ϭ 10) or nicotine (675 Ϯ 166, n ϭ 9), consistent with previous results (Bordia et al., 2008).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bordia et al., 2008 source
Not checked in the free run.
- Findingown data
Mecamylamine at 0.5 and 2.0 mg/kg for 4 days also significantly reduced orolingual and forelimb AIMs.
“A 4-day treatment regimen with 0.5 and 2.0 mg/kg mecamylamine also resulted in significant reductions in orolingual (P Ͻ 0.01) and forelimb (P Ͻ 0.05) AIMs.”
Quote in the paperSubstantial claim - Findingown data
An antagonist alone (mecamylamine) reduced L-DOPA-induced dyskinesias to a similar extent as the agonist nicotine.
“Our studies with mecamylamine also showed that an antagonist alone reduced L-DOPA-induced dyskinesias to a similar extent as the agonist nicotine.”
Quote in the paperSubstantial claim - Findingown data
The combined effects of mecamylamine and nicotine do not result in an additive decrease in L-DOPA-induced AIMs in parkinsonian rats.
“These data show that the combined effects of mecamylamine and nicotine do not result in an additive decrease in L-DOPA-induced AIMs in parkinsonian rats.”
Quote in the paperSubstantial claim - Findingown data
Low doses of nicotine (0.10 and 0.25 mg/kg/day) did not significantly alter L-DOPA-induced AIMs compared with vehicle-treated rats.
“Low doses of nicotine (0.10 and 0.25 mg/kg/day) did not significantly alter L-DOPA-in- duced AIMs compared with vehicle-treated rats (Fig. 7).”
Quote in the paperSubstantial claim - Findingown data
Administered cotinine did not reduce L-DOPA-induced AIMs in the current study.
“The lack of effect of administered cotinine in the current study may be caused by insufficient cotinine entry into the brain such that the CNS levels were too low for efficacy (Lockman et al., 2005).”
Quote in the paperSubstantial claim - Findingown data
There is a very marked decline in α6β2* nAChRs with nigrostriatal damage.
“The current data show that there is a very marked decline in ␣62* nAChRs with nigrostriatal damage.”
Quote in the paperSubstantial claim - Premisecitation
Prior work from the authors' laboratory indicates that nicotine lowers L-DOPA-induced AIMs across multiple parkinsonian animal models.
“Recent studies from our laboratory show that nicotine treatment reduces L-DOPA-induced AIMs in several different parkinsonian animal models (Quik et al., 2008).”
- Also stated in: § Abstract · plain
“We recently showed that nicotine reduces L-DOPA-induced abnormal involuntary movements (AIMs) in parkinsonian animals”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Quik et al., 2008 source
Not checked in the free run.
- Also stated in: § Abstract · plain
- Interpretationown data
The data suggest that nicotine may reduce L-DOPA-induced dyskinesias through nAChR desensitization or block.
“Altogether, the data suggest that nicotine may attenuate L-DOPA-induced dyskinesias via nAChR receptor desensitization or block.”
- Also stated in: § Abstract · hedged
“suggests that the nicotine-mediated improvement in L-DOPA-induced AIMs may involve a desensitization block.”
Quote in the paperSubstantial claim - Also stated in: § Abstract · hedged
- Study design and conductcitation
A 3-day washout was sufficient for L-DOPA-induced AIM scores to return to control values.
“Control studies showed that a 3-day time interval was sufficient for L-DOPA-induced AIM scores to return to control values (Bordia et al., 2008).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bordia et al., 2008 source
Not checked in the free run.
- Interpretationcitation
Optimal reductions in L-DOPA-induced AIMs occur at nicotine doses that produce plasma cotinine levels at the lower end of those seen in smokers.
“Thus, optimal declines in L-DOPA-induced AIMs are obtained with nicotine doses that result in plasma cotinine values at the lower end of those observed in the plasma of smokers (Matta et al., 2007).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Matta et al., 2007 source
Not checked in the free run.
- Study design and conductown data
Repeat experiments using the same doses of a given drug produced a similar decline in L-DOPA-induced AIMs.
“however, repeat experiments with the same doses of a specific drug yielded a similar decline in L-DOPA-induced AIMs.”
Quote in the paperSubstantial claim - Premisecitation
In parkinsonian monkeys, nicotine delivered through drinking water cut L-DOPA-induced dyskinesias by roughly half.
“Nicotine administered via drinking water attenuated L-DOPA-in- duced dyskinesias by approximately 50% in parkinsonian monkeys (Quik et al., 2007).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Quik et al., 2007 source
Not checked in the free run.
- Interpretationreasoning
The combined prior data suggest that nicotine may be a novel pharmacological approach for treating abnormal movements caused by chronic L-DOPA.
“These combined data suggest that nicotine may represent a novel pharmacological approach for treating the abnormal movements that arise with chronic L-DOPA dosing.”
Quote in the paperSubstantial claim - Premisecitation
Comparable decreases in L-DOPA-induced AIMs were seen in parkinsonian rats and mice.
“A similar decline in L-DOPA- induced AIMs was observed in parkinsonian rats (Bordia et al., 2008) and mice (Huang et al., 2009), attesting to the robustness of this effect across species.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Bordia et al., 2008 source
Not checked in the free run.
- cites Huang et al., 2009
Not checked in the free run.
- Premisecitation
Chronic administration of either nicotine or nAChR antagonists results in nAChR up-regulation.
“Moreover, it is well established that chronic administration of either nicotine or nAChR antagonists both result in nAChR up-regulation (Hulihan-Giblin et al., 1990a,b;Kuryatov et al., 2005;Picciotto et al., 2008;Buccafusco et al., 2009).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Interpretationown data
Nicotine exerts its effects through an interaction at nAChRs.
“The results suggest that nicotine exerts its effects through an interaction at nAChRs, nAChR desensitization may play an important role in the observed reduction in L-DOPA-induced dyskinesias, and the long-lasting nicotine metabolite cotinine is not involved in these effects.”
Quote in the paperSubstantial claim - Interpretationown data
The non-additive decline in AIMs with combined nicotine and mecamylamine suggests that nicotine acts through a nAChR interaction.
“The decline in AIMs with combined nicotine and mecamylamine treatment was not additive, suggesting that nicotine exerts its effects via a nAChR interaction.”
Quote in the paperSubstantial claim- Rests on an assumption: Mecamylamine acts as a general nicotinic acetylcholine receptor antagonist.
- Premisecitation
nAChR-subtype agonists decrease L-DOPA-induced dyskinesias in rats.
“This idea is further supported by our studies that show that nAChR-subtype agonists decrease L-DOPA-induced dyskinesias in rats (Campos et al., 2009;Parameswaran et al., 2009).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Campos et al., 2009
Not checked in the free run.
- cites Parameswaran et al., 2009
Not checked in the free run.
- Interpretationreasoning
Nicotine and the antagonist mecamylamine decrease L-DOPA-induced dyskinesias via nAChR blockade.
“These observations suggest that nicotine and the antagonist mecamylamine decrease L-DOPA-induced dyskinesias via nAChR blockade.”
Quote in the paperSubstantial claim- Rests on an assumption: Mecamylamine blocks multiple nAChR subtypes.
- Interpretationown data
The nicotine-mediated improvement in L-DOPA-induced AIMs may involve a desensitization block.
“suggests that the nicotine-mediated improvement in L-DOPA-induced AIMs may involve a desensitization block.”
Quote in the paperSubstantial claim - Interpretationreasoning
Remaining nAChRs are involved in the nicotine-mediated decrease in L-DOPA-induced AIMs.
“Because nicotine treatment reduces abnormal movements in lesioned rats, these data suggest that remaining nAChRs are involved in the nicotine-mediated decrease in L-DOPA-in- duced AIMs.”
Quote in the paperSubstantial claim - Interpretationown data
Nicotine and mecamylamine attenuate AIMs via a shared mechanism of action, that is, by interacting at nAChRs.
“One interpretation of these observations is that nicotine and mecamylamine attenuate AIMs via a shared mechanism of action, that is, by interacting at nAChRs.”
Quote in the paperSubstantial claim- Rests on an assumption: Mecamylamine blocks multiple nAChR subtypes.
- Interpretationcitation
The remaining α4β2 nAChR population is the most likely candidate for mediating nicotine's effect, rather than the α4α5β2 subtype.
“The most likely candidate is the remaining ␣42 nAChR population rather than the ␣4␣52 subtype, because ␣4␣52 nAChRs are localized presynaptically on dopaminergic terminals that are lost with lesioning (Grady et al., 2009).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Grady et al., 2009
Not checked in the free run.
- Interpretationown data
The non-additive effect of nicotine and mecamylamine suggests that they act through a similar mechanism.
“The observation that the effect of nicotine and mecamylamine was not additive suggests that they act via a similar mechanism.”
Quote in the paperSubstantial claim - Interpretationown data
The nicotine-induced decline in L-DOPA-induced AIMs most likely involves longer-term molecular changes in the brain.
“These combined data suggest that the nicotine-induced decline in L-DOPA-induced AIMs most likely involves longer-term molecular changes in the brain.”
- Also stated in: § Abstract · hedged
“Importantly, a single nicotine injection did not reduce AIMs, indicating that nicotine's effect is caused by long-term rather than short-term molecular changes.”
Quote in the paperSubstantial claim - Also stated in: § Abstract · hedged
- Premisecitation
Nicotine reduces L-DOPA-induced AIMs when administered via minipump.
“Our previous work had shown that nicotine also reduced L-DOPA-induced AIMs when given via minipump (Bordia et al., 2008).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bordia et al., 2008 source
Not checked in the free run.
- Interpretationown data
The rat striatal α6β2* nAChR population down-regulated by nicotine is lost with nigrostriatal damage.
“These data suggest that the rat striatal ␣62* nAChR population down-regulated by nicotine is lost with nigrostriatal damage.”
Quote in the paperSubstantial claim - Premisecitation
Nicotine and nAChR blockers may have comparable pharmacological/physiological effects.
“Precedence for the idea that nAChR desensitization makes an important contribution to nicotine's functional effects is evident from previous work showing that nicotine and nAChR blockers may have comparable pharmacological/ physiological effects (Picciotto et al., 2008;Buccafusco et al., 2009).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationown data
nAChR desensitization may play an important role in the reduction of L-DOPA-induced dyskinesias.
“The results suggest that nicotine exerts its effects through an interaction at nAChRs, nAChR desensitization may play an important role in the observed reduction in L-DOPA-induced dyskinesias, and the long-lasting nicotine metabolite cotinine is not involved in these effects.”
Quote in the paperSubstantial claim- Rests on an assumption: Minipump administration results in a slow continual release of nicotine that readily promotes receptor desensitization.
- Interpretationreasoning
Nicotine reduces L-DOPA-induced AIMs by preventing the action of endogenous acetylcholine at CNS nAChRs.
“The idea that a nAChR block either via desensitization or direct antagonism is important would suggest that nicotine reduces L-DOPA- induced AIMs by preventing the action of endogenous acetylcholine at CNS nAChRs.”
Quote in the paperSubstantial claim - Interpretationcitation
The overall behavioral consequences of nicotine may represent a balance between the integrative effects of nAChR activation and subsequent desensitization.
“Thus, the overall behavioral consequences of nicotine may represent a balance between the integrative effects of nAChR activation and subsequent desensitization.”
Quote in the paperSubstantial claim - Interpretationcitation
Desensitization most likely involves post-translational receptor changes including receptor phosphorylation.
“Desensitization most likely involves post-translational receptor changes including receptor phosphorylation (Corringer et al., 2006;Picciotto et al., 2008;Buccafusco et al., 2009).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Interpretationown data
The long-lasting nicotine metabolite cotinine is not involved in the reduction of L-DOPA-induced dyskinesias.
“The results suggest that nicotine exerts its effects through an interaction at nAChRs, nAChR desensitization may play an important role in the observed reduction in L-DOPA-induced dyskinesias, and the long-lasting nicotine metabolite cotinine is not involved in these effects.”
Quote in the paperSubstantial claim - Interpretationown data
The greatest reduction in L-DOPA-induced AIMs was obtained with a nicotine dose yielding plasma cotinine levels at the lower end of those observed in smokers.
“Again, the greatest reduction in L-DOPA-induced AIMs was obtained with a nicotine dose that yielded plasma cotinine levels at the lower end of those observed in the plasma of smokers.”
Quote in the paperSubstantial claim - Interpretationnone given
The neural substrates that influence the nicotine-mediated reduction in L-DOPA-induced dyskinesias most likely involve the nigrostriatal pathway.
“The neural substrates that influence the nicotine-mediated reduction in L-DOPA-induced dyskinesias most likely involve the nigrostriatal pathway.”
Quote in the paperSubstantial claim - Premisecitation
Deep brain stimulation of the subthalamic nucleus reduces dyskinesias.
“Further support for a contribution of other brain areas in L-DOPA-induced AIMs is based on evidence demonstrating beneficial effects of deep brain stimulation of the subthalamic nucleus in reducing dyskinesias (Benabid et al., 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Benabid et al., 2009 source
Not checked in the free run.
- Interpretationcitation
Other brain regions are probably also involved in L-DOPA-induced AIMs because AIMs occur via integrative changes in multiple neurotransmitter systems throughout the CNS.
“However, other brain regions are probably also involved because L-DOPA-induced AIMs occur via integrative changes in multiple neurotransmitter systems throughout the CNS, including those present in the striatum, globus pallidus, thalamus, cortical areas, subthalamic nucleus, and cerebellum (Carta et al., 2008;Fox et al., 2008).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
Intermittent nicotine exposure via drinking water effectively reduces AIMs in both rats and monkeys.
“In addition, our previous data demonstrate that intermittent exposure via drinking water also effectively reduces AIMs in both rats and monkeys (Quik et al., 2007;Bordia et al., 2008).”
Quote in the paperSubstantial claim0 of 2 sources checked
- May combine two claims. 25
- The quote only partly states this claim. 3
- Classified as probably not a substantial claim. 15
May combine two claims.
Findingown dataNicotine at 0.1 mg/kg produced the largest reduction in total, orolingual, and forelimb AIMs, with a trend toward reduced axial AIMs.
“However, 0.1 mg/kg nicotine resulted in a maximal reduction in total, orolingual, and forelimb AIMs with a trend for a decline in axial AIMs.”
- Also stated in: § Abstract · plain
“Dose-ranging studies showed that injection of 0.1 mg/kg nicotine once or twice daily for 4 or 10 days most effectively reduced AIMs, with no worsening of parkinsonism.”
Quote in the paperSubstantial claim- Also stated in: § Abstract · plain
May combine two claims.
Findingown dataHigher nicotine doses of 0.25, 0.5, and 0.75 mg/kg also significantly reduced total, orolingual, and forelimb AIMs, but the reductions appeared smaller than with 0.1 mg/kg.
“Higher doses of nicotine (0.25, 0.5, and 0.75 mg/kg) also resulted in significant reductions in total, orolingual, and forelimb AIMs; however, the declines appeared less pronounced than those observed with the 0.1 mg/kg dose.”
Quote in the paperSubstantial claimThe quote only partly states this claim.
Findingown dataThere was a 99% decline in striatal dopamine transporter in the lesioned striatum compared to the unlesioned striatum.
“The results in Table 3 show that there was a 99% decline in the transporter, as anticipated, attesting to the effectiveness of the lesioning paradigm (Cenci and Lundblad, 2007;Bordia et al., 2008).”
Quote in the paperSubstantial claimMay combine two claims. The quote only partly states this claim.
Findingown dataANOVA showed a significant main effect of nicotine for once-daily 4-day treatment and twice-daily 4-day treatment, a trend for once-daily 10-day treatment, and no effect for the single dose.
“Analyses of variance yielded a significant main effect of nicotine treatment with the once-daily injection (Fig. 4B, p Ͻ 0.05) and twice-daily injection for 4 days (Fig. 4D, p Ͻ 0.01) with a trend for reduction with once-daily treatment for 10 days (Fig. 4C, p Ͻ 0.06).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataMultiday 0.1 mg/kg nicotine decreased L-DOPA-induced AIMs with an approximately similar pattern across treatment regimens.
“Multiday 0.1 mg/kg nicotine treatment (Fig. 4, B-D) decreased L-DOPA-induced AIMs, with an approximately similar pattern in the decline in L-DOPA-induced AIMs with the different treatment regimens.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataMecamylamine at 1.0 mg/kg was optimal, significantly reducing total, orolingual, and forelimb AIMs and showing a trend toward reduced axial AIMs.
“Optimal efficacy was observed with the 1.0 mg/kg dose, with a significant reduction in total (P Ͻ 0.05), orolingual (P Ͻ 0.01), and forelimb (P Ͻ 0.05) and a trend for decline in axial AIMs.”
Quote in the paperSubstantial claimMay combine two claims. The quote only partly states this claim.
Findingown dataCombined nicotine and mecamylamine treatment produced an effect similar to either drug alone, and the effect was not additive.
“Interestingly, the effect of combined treatment with both drugs was similar to that observed with nicotine or mecamylamine on their own (Fig. 6).”
- Also stated in: § Abstract · hedged
“The decline in AIMs with combined nicotine and mecamylamine treatment was not additive, suggesting that nicotine exerts its effects via a nAChR interaction.”
Quote in the paperSubstantial claim- Also stated in: § Abstract · hedged
May combine two claims.
Findingown dataBoth nicotine and mecamylamine significantly increased α4β2* nAChR binding on the unlesioned side, but not the lesioned side, compared with vehicle-treated controls.
“Both drugs significantly increased (p Ͻ 0.01) ␣42* binding on the unlesioned, but not lesioned, side compared with vehicle-treated controls.”
- Also stated in: § Discussion · plain
“The agonist and antagonist also both increased ␣42* nAChRs in the unlesioned, but not lesioned, striatum.”
Quote in the paperSubstantial claim- Also stated in: § Discussion · plain
May combine two claims.
Findingown dataL-DOPA-induced AIMs plateau within 60 minutes after injection and then gradually decline.
“The time course data in Fig. 4 show that L-DOPA-induced AIMs plateau within 60 min after injection and then gradually decline.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataNicotine or mecamylamine treatment both decreased α6β2* and increased α4β2* nAChR expression.
“This latter finding, combined with data showing that mecamylamine reduced AIMs to a similar extent as nicotine, and that nicotine or mecamylamine treatment both decreased ␣62* and increased ␣42* nAChR expression, suggests that the nicotine-mediated improvement in L-DOPA-induced AIMs may involve a desensitization block.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataNicotine given intermittently via multiday injection or constantly via minipump for several days both attenuate L-DOPA-induced AIMs in parkinsonian rats.
“They show that nicotine given intermittently via multiday injection or constantly via minipump for several days both attenuate L-DOPA-induced AIMs in parkinsonian rats, an animal model predictive of the human condition.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationDeep brain stimulation is an alternative management approach for L-DOPA-induced dyskinesias but is a serious surgical intervention with associated risks.
“An alternate approach for the management of L-DOPA-induced dyskinesias in Parkinson's disease involves deep brain stimulation; however, this is a serious surgical intervention with associated risks (Benabid et al., 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Benabid et al., 2009 source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationNicotine generally acts in the central nervous system through nicotinic acetylcholine receptors.
“Nicotine generally exerts its effects in the central nervous system (CNS) via an interaction at nicotinic acetylcholine receptors (nAChRs) (Albuquerque et al., 2009;Gotti et al., 2009).”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationA smaller population of α6β2* nAChRs is restricted to CNS catecholaminergic neurons, including nigrostriatal neurons, and may be involved in reward, addiction, and motor activity.
“There is also a smaller population of ␣62* nAChRs, which is restricted in localization to CNS catecholaminergic neurons, including those in the nigrostriatal pathway, which may be involved in reward, addiction, and motor activity (Drenan et al., 2008;Pons et al., 2008).”
Quote in the paperNot a substantial claim0 of 2 sources checkedClassified as probably not a substantial claim.
Study design and conductown dataAt baseline, lesioned rats were randomly divided into two groups with comparable total L-DOPA-induced AIM scores.
“At the beginning of the study, lesioned rats were randomly divided into two groups such that total L-DOPA-induced AIM scores were comparable in the two sets of animals (62.9 Ϯ 6.6 and 60.5 Ϯ 10.4).”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
PremisecitationThe α4β2*, α6β2*, and α7 nAChR subtypes have been implicated in striatal function and influence striatal dopamine release.
“All three nAChR subtypes (␣42*, ␣62*, and ␣7) have been implicated in striatal function and shown to influence striatal dopamine release (Grady et al., 2007).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Grady et al., 2007 source
Not checked in the free run.
May combine two claims.
PremisecitationNicotinic regulation of dopamine release likely involves an interplay between receptor activation and desensitization, and desensitization produces an effective channel block similar to that seen with nAChR antagonists.
“In addition, studies using cyclic voltametry indicate that this regulation of dopamine release most likely represents a complex interplay between nicotinic receptor activation and desensitization (Exley et al., 2008;Meyer et al., 2008;Perez et al., 2008)”
- Also stated in: § Abstract · plain
“with the latter resulting in an effective channel block similar to that observed with nAChR antagonists (Corringer et al., 2006;Picciotto et al., 2008;Buccafusco et al., 2009).”
Quote in the paperSubstantial claim0 of 3 sources checked- Also stated in: § Abstract · plain
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationDyskinesias occur in most patients after repeated L-DOPA exposure and can be troublesome or disabling.
“These excessive abnormal involuntary movements (AIMs), which occur in the majority of patients with repeated exposure to L-DOPA, can be very troublesome and even disabling (Fahn, 2008;Schapira et al., 2009).”
Quote in the paperNot a substantial claim0 of 2 sources checkedClassified as probably not a substantial claim.
PremisecitationFew drugs are currently available to reduce dyskinesias.
“Few drugs are currently available to attenuate dyskinesias (Fahn, 2008;Schapira et al., 2009).”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe agonist nicotine and the antagonist mecamylamine both exert antidepressant-like effects.
“Behavioral studies also show that the agonist nicotine and the antagonist mecamylamine both improve memory-related task performance in rodents and monkeys (Buccafusco and Jackson, 1991;Terry et al., 1999) and exert antidepressant-like effects (Semba et al., 1998;Tizabi et al., 1998;Shytle et al., 2002;Gatto et al., 2004).”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
InterpretationcitationNicotine exposure may slowly stabilize nAChRs in a high-affinity state that is more easily activated, leading eventually to desensitization.
“Alternatively, or as well, nicotine exposure may slowly stabilize nAChRs in a high-affinity state that is more easily activated, leading eventually to desensitization (Vallejo et al., 2005).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Vallejo et al., 2005 source
Not checked in the free run.
May combine two claims.
Premisecitationα4β2* nAChRs in the striatum are 80% localized postsynaptically on GABAergic neurons where they modulate GABA release and 20% presynaptically on dopaminergic terminals involved in regulating dopamine release.
“In addition, they are present in the striatum, with 80% localized postsynaptically on GABAergic neurons where they modulate GABA release and 20% presynaptically on dopaminergic terminals that are involved in regulating dopamine release (Grady et al., 2007;Quik et al., 2008).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationNicotine initially activates and then subsequently desensitizes or inactivates nAChRs, with a consequent receptor block.
“The molecular basis for these seemingly discrepant observations may relate to findings that nicotine initially activates and then subsequently desensitizes or inactivates nAChRs, with a consequent receptor block (Corringer et al., 2006;Picciotto et al., 2008;Buccafusco et al., 2009).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
Interpretationown dataThe similarity in changes in α6β2* and α4β2* nAChRs with nicotine and mecamylamine treatment with and without nigrostriatal damage suggests a similarity in mechanism of action, that is, that nicotine induces its effects via a receptor desensitization blockade.
“The similarity in the changes in ␣62* and ␣42* nAChRs with nicotine and mecamylamine treatment with and without nigrostriatal damage suggests a similarity in mechanism of action, that is, that nicotine induces its effects via a receptor desensitization blockade.”
Quote in the paperSubstantial claim- Rests on an assumption: Mecamylamine blocks multiple nAChR subtypes.
- Rests on an assumption: Minipump administration results in a slow continual release of nicotine that readily promotes receptor desensitization.
May combine two claims.
PremisecitationThe agonist nicotine and the antagonist mecamylamine both improve memory-related task performance in rodents and monkeys.
“Behavioral studies also show that the agonist nicotine and the antagonist mecamylamine both improve memory-related task performance in rodents and monkeys (Buccafusco and Jackson, 1991;Terry et al., 1999) and exert antidepressant-like effects (Semba et al., 1998;Tizabi et al., 1998;Shytle et al., 2002;Gatto et al., 2004).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Buccafusco and Jackson, 1991
Not checked in the free run.
- cites Terry et al., 1999 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationCotinine exhibits several nicotinelike properties, including effects on acoustic startle, attention, and neuroprotection.
“Indeed, studies show that cotinine exhibits several nicotinelike properties, including effects on acoustic startle, attention, and neuroprotection (Buccafusco and Terry, 2003;Buccafusco et al., 2009).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Buccafusco and Terry, 2003
Not checked in the free run.
- cites Buccafusco et al., 2009 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationCotinine is a primary nicotine metabolite with an extensive half-life (17-18 h).
“One such compound is cotinine, a primary nicotine metabolite with an extensive half-life (17-18 h) (Matta et al., 2007).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Matta et al., 2007 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Interpretationcitationα6β2* nAChRs localized to catecholaminergic neurons may also be relevant for the observed effects of nicotine on L-DOPA-induced AIMs.
“The ␣62* nAChRs localized to catecholaminergic neurons may also be of relevance for the observed effects of nicotine on L-DOPA-induced AIMs (Grady et al., 2007;Quik et al., 2008).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationThe lack of effect of administered cotinine may be due to insufficient cotinine entry into the brain, with CNS levels too low for efficacy.
“The lack of effect of administered cotinine in the current study may be caused by insufficient cotinine entry into the brain such that the CNS levels were too low for efficacy (Lockman et al., 2005).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Lockman et al., 2005 source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
PremisecitationCotinine stimulates nAChRs and may have biological effects.
“The rather high circulating plasma cotinine levels after nicotine ingestion, coupled with findings that cotinine stimulates nAChRs, has prompted the suggestion that cotinine per se may have biological effects (Dwoskin et al., 1999;O'Leary et al., 2008).”
Quote in the paperSubstantial claim0 of 2 sources checkedClassified as probably not a substantial claim.
PremisecitationNicotine formulations (patch, gum, lozenge, nasal spray, nasal inhalant) are currently available in humans for smoking cessation.
“This includes the nicotine patch, gum, lozenge, nasal spray, and nasal inhalant (Matta et al., 2007).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Matta et al., 2007 source
Not checked in the free run.
Classified as probably not a substantial claim.
InterpretationreasoningAny of these nicotine applications has potential in the treatment of L-DOPA-induced dyskinesias.
“Our data would suggest that any one of these applications has potential in the treatment of L-DOPA-induced dyskinesias.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningNicotine consistently reduced L-DOPA-induced AIMs across species, using several different treatment paradigms.
“Thus, nicotine consistently reduced L-DOPA-induced AIMs across species, using several different treatment paradigms.”
Quote in the paperSubstantial claim
The paper relies on this without support.
Mecamylamine acts as a general nicotinic acetylcholine receptor antagonist.
“Because mecamylamine is a well known nAChR antagonist”
“mecamylamine is a nonspecific nAChR antagonist that blocks ganglionic nicotinic receptors.”
The paper relies on this without support.
The present work is the first to investigate mechanisms of nicotine-mediated decline in L-DOPA-induced dyskinesias.
“The present work is the first to investigate the potential mechanisms of nicotine-mediated decline in L-DOPA-induced dyskinesias.”
The paper relies on this without support.
Mecamylamine blocks multiple nAChR subtypes.
“mecamylamine, an antagonist that blocks multiple nAChR subtypes.”
The paper relies on this without support.
Minipump administration results in a slow continual release of nicotine that readily promotes receptor desensitization.
“This latter mode of administration results in a slow continual release of nicotine that readily promotes receptor desensitization.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Nicotine and other nAChR agonists induce their behavioral effects via nAChR desensitization.
“This idea is consistent with an extensive literature suggesting that nicotine and other nAChR agonists induce their behavioral effects via this mechanism (Picciotto et al., 2008;Buccafusco et al., 2009;Bordia et al., 2010;Mineur and Picciotto, 2010;Grady et al., 2012).”
From Varenicline Is a Potent Partial Agonist at α6β2* Nicotinic Acetylcholine Receptors in Rat and Monkey Striatum (2012) · cites this paper as Bordia et al., 2010
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Conflicting timing of nicotine injection before L-DOPA
MajorThe methods say nicotine was injected 10 minutes before L-DOPA, but the Figure 6 caption says the listed treatments, including nicotine, were followed 30 minutes later by L-DOPA.
“In one series of experiments, mecamylamine (0.5-2 mg/kg; Sigma-Aldrich) and/or nicotine (0.01-0.75 mg/kg; freebase; Sigma-Aldrich) were injected 30 and 10 min before L-DOPA/benserazide treatment, respectively”
“Stably dyskinetic 6-OHDA-lesioned rats were injected with saline, mecamylamine (1 mg/ kg), nicotine (0.1 mg/kg), or mecamylamine (1 mg/kg) ϩ nicotine (0.1 mg/kg), followed 30 min later by L-DOPA.”
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“Desensitization most likely involves post-translational receptor changes including receptor phosphorylation (Corringer et al., 2006; Picciotto et al., 2008; Buccafusco et al., 2009).”
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Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson's disease
Bastide, M. F., Meissner, W. G., Picconi, B., Fasano, S., Fernagut, P., Feyder, M. T., Francardo, V., Alcacer, C., Ding, Y., Brambilla, R., et al. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.07.002 · Cited by 470 · see citing works
“cotine best reduced LID in animal models with a moderate grostriatal loss (Bordia et al., 2010; Quik et al., 2013c), suggesting”
BackgroundSelf-citationThe Pharmacology of l-DOPA-Induced Dyskinesia in Parkinson’s Disease
Huot, P., Johnston, T. H., Koprich, J. B., Fox, S. H., & Brotchie, J. M. (2013) · Pharmacological Reviews · doi:10.1124/pr.111.005678 · Cited by 324 · see citing works
“Following the unexpected discovery that chronic therapy with either nicotinic agonists or antagonists alleviates LID, it was proposed that nicotine alleviated dyskinesia after a desensitization phenomenon that would occur upon chronic administration (Bordia et al., 2010).”
BackgroundStriatal cholinergic interneuron regulation and circuit effects
Lim, S. A. O., Kang, U. J., & McGehee, D. S. (2014) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2014.00022 · Cited by 236 · see citing works
“Treatment with either nAChR antagonists or nicotine improves abnormal involuntary movements (AIMs) in rodents and primates, which suggests that both drugs are decreasing nAChR function either through receptor blockade or desensitization (Quik et al., 2007; Bordia et al., 2010; Zhang et al., 2013).”
BackgroundNicotine as a potential neuroprotective agent for Parkinson's disease
Quik, M., Perez, X. A., & Bordia, T. (2012) · Movement Disorders · doi:10.1002/mds.25028 · Cited by 242 · see citing works
Self-citationDeficits in cholinergic neurotransmission and their clinical correlates in Parkinson’s disease
Perez‐Lloret, S., & Barrantes, F. J. (2016) · npj Parkinson s Disease · doi:10.1038/npjparkd.2016.1 · Cited by 212 · see citing works
“The mechanism by which nicotine might reduce LIDs was further explored in a study on 6OHDA-lesioned rats.(75) Interestingly, in addition to the already known antidyskinetic effect of nicotine, mecamylamine, a nicotinic receptor blocker, also reduced LIDs.”
Backgroundα6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson’s Disease
Quik, M., & Wonnacott, S. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.003269 · Cited by 194 · see citing works
Self-citationDrenan, R. M., Grady, S. R., Steele, A. D., McKinney, S., Patzlaff, N. E., McIntosh, J. M., Marks, M. J., Miwa, J. M., & Lester, H. A. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2056-10.2010 · Cited by 127 · see citing works
“For example, stimulating DA release with α6α4β2* selective compounds in PD may alleviate dyskinesias associated with LDopa therapy if co-administration of the nAChR compound allowed the clinician to reduce the necessary dose of L-Dopa (Quik and McIntosh, 2006; Quik et al., 2008; Bordia et al., 2010).”
Self-citationAlpha7 nicotinic receptors as therapeutic targets for Parkinson’s disease
Quik, M., Zhang, D., McGregor, M., & Bordia, T. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.06.014 · Cited by 113 · see citing works
Self-citationNovel nondopaminergic targets for motor features of Parkinson's disease: Review of recent trials
Kalia, L., Brotchie, J., & Fox, S. H. (2013) · Movement Disorders · doi:10.1002/mds.25273 · Cited by 116 · see citing works
“1); thus, chronic treatment with a nicotinic agonist appears to be required to reduce dyskinesia.(24) Presently, oral small-molecule nicotinic”
BackgroundNicotine from cigarette smoking and diet and Parkinson disease: a review
Ma, C., Liu, Y., Neumann, S., & Gao, X. (2017) · Translational Neurodegeneration · doi:10.1186/s40035-017-0090-8 · Cited by 101 · see citing works
“With respect to hemiparkinsonian rats, which received levodopa injection, nicotine also reduced dyskinesia by more than 50% [78, 79].”
BackgroundAnimal models of l ‐dopa‐induced dyskinesia in Parkinson's disease
Cenci, M. A., & Crossman, A. R. (2018) · Movement Disorders · doi:10.1002/mds.27337 · Cited by 98 · see citing works
Striatal Cholinergic Cell Ablation Attenuates l-DOPA Induced Dyskinesia in Parkinsonian Mice
Won, L., Ding, Y., Singh, P., & Kang, U. J. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.2888-13.2014 · Cited by 89 · see citing works
“…roles of striatal cholinergic neurons in basal ganglia function include the efficacy of muscarinic antagonist, dicyclomine in reducing previously established LID in PD mouse models (Ding et al., 2011) and effect of nicotinic receptor inhibition on LID in hemiparkinsonian rats (Bordia et al., 2010).”
BackgroundQuik, M., Perez, X. A., & Grady, S. R. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.06.001 · Cited by 94 · see citing works
Self-citationOptogenetic activation of striatal cholinergic interneurons regulates L-dopa-induced dyskinesias
Bordia, T., Perez, X. A., Heiss, J. E., Zhang, D., & Quik, M. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.02.019 · Cited by 87 · see citing works
Self-citationAmantadine: reappraisal of the timeless diamond—target updates and novel therapeutic potentials
Danysz, W., Dekundy, A., Scheschonka, A., & Riederer, P. F. (2021) · Journal of Neural Transmission · doi:10.1007/s00702-021-02306-2 · Cited by 85 · see citing works
“Furthermore, similar effects were found after nicotine agonists, but were attributed to receptor desensitization effect (Bordia et al. 2010).”
BackgroundResultHuang, L. Z., Campos, C., Ly, J., Carroll, F. I., & Quik, M. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.12.032 · Cited by 73 · see citing works
“) for 3 wk until they were stably dyskinetic as assessed using an established AIMs rating scale (Bordia et al., 2010; Cenci and Lundblad, 2007).”
InfluentialSelf-citationBordia, T., Hrachova, M., Chin, M., McIntosh, J. M., & Quik, M. (2012) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.194852 · Cited by 70 · see citing works
“This idea is consistent with an extensive literature suggesting that nicotine and other nAChR agonists induce their behavioral effects via this mechanism (Picciotto et al., 2008; Buccafusco et al., 2009; Bordia et al., 2010; Mineur and Picciotto, 2010; Grady et al., 2012).”
ResultSelf-citationNicotine Reduces l-DOPA-Induced Dyskinesias by Acting at β2* Nicotinic Receptors
Huang, L. Z., Grady, S. R., & Quik, M. (2011) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.111.182949 · Cited by 70 · see citing works
“Evidence for this stems from studies showing that the nonselective nAChR blocker mecamylamine modulated L-DOPA-induced AIMs in rats (Bordia et al., 2010) and that nonselective nAChR agonists reduce L-DOPAinduced AIMs (Huang et al., 2011).”
InfluentialSelf-citationBordia, T., McGregor, M. M., Papke, R. L., Decker, M. W., McIntosh, J. M., & Quik, M. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.09.015 · Cited by 67 · see citing works
Self-citationNicotine and Nicotinic Receptor Drugs
Quik, M., Bordia, T., Zhang, D., & Perez, X. A. (2015) · International review of neurobiology · doi:10.1016/bs.irn.2015.07.005 · Cited by 66 · see citing works
Self-citationRole for the nicotinic cholinergic system in movement disorders; therapeutic implications
Quik, M., Zhang, D., Perez, X. A., & Bordia, T. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.05.004 · Cited by 62 · see citing works
Self-citationNicotine reduces established levodopa‐induced dyskinesias in a monkey model of Parkinson's disease
Quik, M., Mallela, A., Ly, J., & Zhang, D. (2013) · Movement Disorders · doi:10.1002/mds.25594 · Cited by 60 · see citing works
“movements (AIMs) in both 6-hydroxydopaminelesioned mice and rats.(10,11,13) The nicotine-mediated”
BackgroundInfluentialSelf-citationNeuronal nicotinic receptor agonists improve gait and balance in olivocerebellar ataxia
Wecker, L., Engberg, M. E., Philpot, R. M., Lambert, C. S., Kang, C. W., Antilla, J. C., Bickford, P. C., Hudson, C. E., Zesiewicz, T. A., & Rowell, P. P. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.05.016 · Cited by 46 · see citing works
“Further, based on studies demonstrating that both nicotine and mecamylamine ameliorated the induced abnormal involuntary movements in these rats to a similar extent, Bordia et al. (2010) suggested that the beneficial effects of nicotine may involve desensitization of neuronal nicotinic receptors.”
BackgroundMethodInfluentialSchaeffer, E., Pilotto, A., & Berg, D. (2014) · CNS Drugs · doi:10.1007/s40263-014-0205-z · Cited by 54 · see citing works
A new outlook on cholinergic interneurons in Parkinson’s disease and L-DOPA-induced dyskinesia
Conti, M. M., Chambers, N., & Bishop, C. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.05.021 · Cited by 47 · see citing works
Zhang, D., Mallela, A., Sohn, D., Carroll, F. I., Bencherif, M., Letchworth, S. R., & Quik, M. (2013) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.207639 · Cited by 49 · see citing works
“Tolerance to the effect of nicotine did not develop in any species with study periods up to 6 months (Quik et al., 2007; Bordia et al., 2008, 2010; Huang et al., 2011a).”
BackgroundInfluentialSelf-citationQuik, M., Campos, C., & Grady, S. R. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.06.027 · Cited by 49 · see citing works
“However, its effects on AIMs were not additive with those of nicotine, further suggesting that nicotine acts at nAChRs [22].”
Self-citationPathophysiological Mechanisms and Experimental Pharmacotherapy for L-Dopa-Induced Dyskinesia
Fabbrini, A., & Guerra, A. (2021) · Journal of Experimental Pharmacology · doi:10.2147/jep.s265282 · Cited by 47 · see citing works
ABT‐089 and ABT‐894 reduce levodopa‐induced dyskinesias in a monkey model of Parkinson's disease
Zhang, D., Bordia, T., McGregor, M. M., McIntosh, J. M., Decker, M. W., & Quik, M. (2014) · Movement Disorders · doi:10.1002/mds.25817 · Cited by 45 · see citing works
Self-citationLevodopa-induced dyskinesias in Parkinson’s disease: emerging treatments
Konitsiotis, S., & Bargiotas, P. (2013) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s36693 · Cited by 45 · see citing works
Quik, M., Mallela, A., Chin, M. C., McIntosh, J. M., Perez, X. A., & Bordia, T. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.09.006 · Cited by 45 · see citing works
“Nicotine also reduced L-dopa-induced abnormal involuntary movements in rodents, when given via several modes of administration, including drinking water, minipumps or injection (Bordia et al., 2008, 2010; Huang et al., 2011a, 2011b).”
BackgroundSelf-citationEnhanced histamine H2 excitation of striatal cholinergic interneurons in l-DOPA-induced dyskinesia
Lim, S. A. O., Xia, R., Ding, Y., Won, L., Ray, W. J., Hitchcock, S. A., McGehee, D. S., & Kang, U. J. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.01.003 · Cited by 43 · see citing works
“Dyskinetic 6-OHDA lesioned rats chronically treated with the non-selective neuronal nicotinic receptor antagonist mecamylamine display a dramatic reduction in abnormal involuntary movements (Bordia et al., 2010).”
Quik, M., Campos, C., Bordia, T., Strachan, J., Zhang, J., McIntosh, J. M., Letchworth, S. R., & Green-Jordan, K. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.03.038 · Cited by 43 · see citing works
“Nicotine, a drug that acts at nicotinic acetylcholine receptors (nAChRs), also reduces L-dopa-induced dyskinetic-like movements in parkinsonian rats, mice and nonhuman primates, without affecting the antiparkinsonian effect of L-dopa (Bordia et al., 2008; Bordia et al., 2010; Huang et al., 2011a; Quik et al., 2007).”
BackgroundMethodResultInfluentialSelf-citationKljakic, O., Janíčková, H., Prado, V. F., & Prado, M. A. M. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14003 · Cited by 39 · see citing works
“Furthermore, chronic application of nicotine can attenuate LID in monkey, rat and mouse models of PD, as repeated exposure to nicotine desensitizes nicotinic receptors thereby decreasing cholinergic tone (Quik et al., 2007; Bordia et al. 2008, 2010).”
BackgroundDevelopmental Nicotine Exposure Alters Neurotransmission and Excitability in Hypoglossal Motoneurons
Pilarski, J. Q., Wakefield, H. E., Fuglevand, A. J., Levine, R. B., & Fregosi, R. F. (2010) · Journal of Neurophysiology · doi:10.1152/jn.00876.2010 · Cited by 40 · see citing works
Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders
Quik, M., Boyd, J. T., Bordia, T., & Perez, X. A. (2018) · Nicotine & Tobacco Research · doi:10.1093/ntr/nty063 · Cited by 38 · see citing works
Self-citationDystonia and levodopa-induced dyskinesias in Parkinson's disease: Is there a connection?
Calabresi, P., & Standaert, D. G. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104579 · Cited by 39 · see citing works
Johnston, T. H., Huot, P., Fox, S. H., Koprich, J. B., Szeliga, K. T., James, J. W., Graef, J. D., Letchworth, S. R., Green-Jordan, K., Hill, M. P., et al. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.06.005 · Cited by 40 · see citing works
“This is in keeping with a lack of anti-dyskinetic effect of acute nicotine administration and the concept that nicotine mediates its antidyskinetic effects via desensitisation of nAChR populations rather than an increase in function effect (Bordia et al., 2010).”
BackgroundCan therapeutic strategies prevent and manage dyskinesia in Parkinson’s disease? An update
Leta, V., Jenner, P. G., Chaudhuri, К. R., & Antonini, A. (2019) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2019.1681966 · Cited by 39 · see citing works
“Nicotine has been shown to reduce LID in rodents [91] and nonhuman primates [92], likely by decreasing dopamine release after a chronic desensitization of nicotinic receptors [93]; however, these findings have not been translated in clinical settings [94,95].”
BackgroundRole for α6 nicotinic receptors in l-dopa-induced dyskinesias in parkinsonian mice
Quik, M., Park, K. M., Hrachova, M., Mallela, A., Huang, L. Z., McIntosh, J. M., & Grady, S. R. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.04.029 · Cited by 37 · see citing works
Self-citationCarvajal-Oliveros, A., Domínguez-Baleón, C., Zárate, R. V., Campusano, J. M., Narváez‐Padilla, V., & Reynaud, E. (2021) · Scientific Reports · doi:10.1038/s41598-021-88910-4 · Cited by 34 · see citing works
Mucuna pruriens seeds in treatment of Parkinson’s disease: pharmacological review
Kasture, S. B., Mohan, M., & Kasture, V. S. (2013) · Oriental Pharmacy and Experimental Medicine · doi:10.1007/s13596-013-0126-2 · Cited by 36 · see citing works
Targeting Nicotinic Receptors for Parkinson's Disease Therapy
Quik, M., Bordia, T., Huang, L. Z., & Perez, X. A. (2011) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152711797247849 · Cited by 37 · see citing works
Self-citationBordia, T., Zhang, D., Perez, X. A., & Quik, M. (2016) · Experimental Neurology · doi:10.1016/j.expneurol.2016.09.009 · Cited by 32 · see citing works
“The effect of mecamylamine was evaluated 30 min after injection consistent with previous work (Bordia et al., 2010; Bordia et al., 2016; Dekundy et al., 2007).”
Self-citationReceptor Ligands as Helping Hands to L-DOPA in the Treatment of Parkinson’s Disease
Bello, F. D., Giannella, M., Giorgioni, G., Piergentili, A., & Quaglia, W. (2019) · Biomolecules · doi:10.3390/biom9040142 · Cited by 32 · see citing works
“Interestingly, similar effects were observed with the non‐selective nicotinic receptor antagonist Mecamylamine [306,310].”
BackgroundInfluentialCholinergic Receptor Modulation as a Target for Preventing Dementia in Parkinson’s Disease
Iarkov, A., Mendoza, C., & Echeverrı́a, V. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.665820 · Cited by 34 · see citing works
“For this reason, modulators of the nAChRs may act as preventative drugs against PD deserve more in-depth consideration (Parain et al., 2001, 2003; Soto-Otero et al., 2002; Bordia et al., 2008; O’Leary et al., 2008; Riveles et al., 2008; Hong et al., 2009; Huang et al., 2009, 2011b; Bordia et al., 2010; Quik et al., 20…”
Backgroundα7 nicotinic receptor agonists reduce levodopa‐induced dyskinesias with severe nigrostriatal damage
Zhang, D., McGregor, M. M., Bordia, T., Perez, X. A., McIntosh, J. M., Decker, M. W., & Quik, M. (2015) · Movement Disorders · doi:10.1002/mds.26453 · Cited by 29 · see citing works
Self-citationPET Molecular Imaging Research of Levodopa-Induced Dyskinesias in Parkinson’s Disease
Pagano, G., Yousaf, T., & Politis, M. (2017) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-017-0794-2 · Cited by 28 · see citing works
“In preclinical studies, elevated cholinergic signalling has been associated with LIDs [72], and muscarinic and nicotinic receptor antagonists partially attenuated the expression of LIDs [73, 74].”
BackgroundThe striatal cholinergic system in l-dopa-induced dyskinesias
Perez, X. A., Bordia, T., & Quik, M. (2018) · Journal of Neural Transmission · doi:10.1007/s00702-018-1845-9 · Cited by 24 · see citing works
“Interestingly, treatment with the general nAChR antagonist mecamylamine also decreased LIDs to a similar extent as that observed with nAChR agonists (Bordia et al. 2010) (Table 2).”
ResultSelf-citationCholinergic control of striatal neurons to modulate L‐dopa‐induced dyskinesias
Bordia, T., & Perez, X. A. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14048 · Cited by 25 · see citing works
“Consistent with previous studies, mecamylamine (Bordia et al., 2010) but not atropine treatment led to a significant decrease in AIMs (Bordia et al.”
BackgroundMethodResultInfluentialSelf-citationProbing striatal microcircuitry to understand the functional role of cholinergic interneurons
Girasole, A. E., & Nelson, A. (2015) · Movement Disorders · doi:10.1002/mds.26340 · Cited by 23 · see citing works
“Finally, several studies have found that chronic treatment with nicotine or nicotinic drugs can ameliorate LID in multiple animal models.(104,105) Together, such studies suggest that cholinergic interneurons and their signaling pathways are potential targets for future therapeutic development.”
BackgroundNicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats
Bordia, T., McIntosh, J. M., & Quik, M. (2011) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.111.189100 · Cited by 25 · see citing works
“Similar results were obtained in parkinsonian rat and mouse models of L-dopa-induced dyskinesias, attesting to the robustness of the effect of nicotine across species (Bordia et al., 2008; Bordia et al., 2010; Huang et al., 2011a; Huang et al., 2011b).”
BackgroundResultSelf-citationPreclinical Evidence for a Role of the Nicotinic Cholinergic System in Parkinson’s Disease
Perez, X. A. (2015) · Neuropsychology Review · doi:10.1007/s11065-015-9303-z · Cited by 25 · see citing works
“Experiments with the non-specific nAChR agonist varenicline as well as with the general nAChR blocker mecamylamine have yielded similar results (Bordia et al. 2010; Huang et al. 2011a) (Table 3).”
ResultEmerging preclinical pharmacological targets for Parkinson's disease
More, S. V., & Choi, D. (2016) · Oncotarget · doi:10.18632/oncotarget.8104 · Cited by 23 · see citing works
“com/oncotarget decrease in LIDs in parkinsonian rodents and monkeys, indicating efficacy across species [52, 71-74].”
BackgroundBordia, T., McIntosh, J. M., & Quik, M. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12179 · Cited by 23 · see citing works
“Notably, a nAChR antagonist mecamylamine also reduced LIDs (Bordia et al. 2010).”
BackgroundMethodResultInfluentialSelf-citationThe Rodent Models of Dyskinesia and Their Behavioral Assessment
Peng, Q., Zhong, S., Tan, Y., Zeng, W., Wang, J., Cheng, C., Yang, X., Wu, Y., Cao, X., & Xu, Y. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.01016 · Cited by 22 · see citing works
Cholinergic activity and levodopa‐induced dyskinesia: a multitracer molecular imaging study
Brumberg, J., Küsters, S., Al‐Momani, E., Marotta, G., Cosgrove, K., van Dyck, C. H., Herrmann, K., Homola, G. A., Pezzoli, G., Buck, A. K., et al. (2017) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.438 · Cited by 19 · see citing works
“Increasing evidence also suggests that nicotine and agonists of the nicotinic acetylcholine receptors (nAChRs) reduce LIDs via nAChRs desensitization.(8) To further examine the role of striatal cholinergic and dopaminergic interplay in LIDs expression, as well as related brain glucose metabolic changes, we investigate…”
Inden, M., Takata, K., Yanagisawa, D., Ashihara, E., Tooyama, I., Shimohama, S., & Kitamura, Y. (2016) · Neurochemistry International · doi:10.1016/j.neuint.2016.02.008 · Cited by 18 · see citing works
Xie, C., Pan, J., Zhang, S., Gan, J., & Liu, Z. (2014) · Neurological Sciences · doi:10.1007/s10072-014-1652-5 · Cited by 19 · see citing works
Bordia, T., McGregor, M., McIntosh, J. M., Drenan, R. M., & Quik, M. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.03.040 · Cited by 17 · see citing works
Self-citationEffect of Nicotine on the Pharmacokinetics of Levodopa
Kyaw, W. T., Nagai, M., Kaneta, M., Kubo, M., Nishikawa, N., Tsujii, T., Iwaki, H., & Nomoto, M. (2013) · Clinical Neuropharmacology · doi:10.1097/wnf.0b013e31827fd9cd · Cited by 17 · see citing works
“Nicotine reduced dyskinesia by more than 50% in 6-hydroxydopamineYinduced hemiparkinsonian rats, which received levodopa injection.(23,24) In another study with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys,(25) nicotine decreased LID occurrence from levodopa and carbidopa treatment by approxima…”
BackgroundAnatomy of graft-induced dyskinesias: Circuit remodeling in the parkinsonian striatum
Steece‐Collier, K., Rademacher, D. J., & Soderstrom, K. E. (2012) · Basal Ganglia · doi:10.1016/j.baga.2012.01.002 · Cited by 17 · see citing works
Focus on α4β2* and α6β2* nAChRs for Parkinson's Disease Therapeutics.
Perez, X. A., & Quik, M. (2011) · PubMed · Cited by 12 · see citing works
Self-citationEffects of antidyskinetic nicotine treatment on dopamine release in dorsal and ventral striatum
Leino, S., Koski, S. K., Rannanpää, S., & Salminen, O. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.02.042 · Cited by 10 · see citing works
Strachan, J., Kombo, D. C., Mazurov, A. A., Heemstra, R. J., Bhatti, B. S., Akireddy, R., Murthy, S. M., Miao, L., Jett, J. E., Speake, J. D., et al. (2014) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2014.08.019 · Cited by 10 · see citing works
Nondopaminergic Treatments for Parkinson’s Disease
Huot, P., & Fox, S. H. (2011) · Neurodegenerative Disease Management · doi:10.2217/nmt.11.62 · Cited by 10 · see citing works
Chen, Y.-H., Kuo, T., Huang, E. Y., Chou, Y., Chiang, Y. H., Hoffer, B. J., & Miller, J. (2018) · Oncotarget · doi:10.18632/oncotarget.24245 · Cited by 7 · see citing works
The dual role of striatal interneurons: circuit modulation and trophic support for the basal ganglia
Wegman, E., Wosiski‐Kuhn, M., & Luo, Y. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.382987 · Cited by 7 · see citing works
“…have shown that striatal ChI contribute to movement abnormalities and LID development in rodent models of PD (Ding et al., 2011; Won et al., 2014; Aldrin-Kirk et al., 2018) and treatment with nicotine or nicotinic drugs ameliorated LID in multiple models (Quik et al., 2007; Bordia et al., 2010).”
BackgroundChristie, L. A., Brice, N., Rowland, A., Dickson, L., Anand, R., Teall, M. R., Doyle, K. J., Narayana, L., Mitchell, C., Harvey, J. R. M., et al. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c00630 · Cited by 5 · see citing works
Experimental Models of l-DOPA-Induced Dyskinesia
Johnston, T. H., & Lane, E. L. (2011) · International review of neurobiology · doi:10.1016/b978-0-12-381328-2.00003-1 · Cited by 4 · see citing works
Symptoms of Parkinson's Disease
Rana, A. Q. (2011) · InTech eBooks · doi:10.5772/953 · Cited by 4 · see citing works
Pathophysiology of Drug-Induced Dyskinesias
Christopher, A., Shivkumar, V., Timothy, P., et al. (2011) · InTech eBooks · doi:10.5772/17248 · Cited by 3 · see citing works
“receptor antagonist mecamylamine can also provide similar effects (Quik et al., 2007; Bordia et al., 2008; Bordia et al., 2010).”
BackgroundKesoyan., A. A., Arakelyan, N. L., Aloyan, D. A., Karapetyan, A. A., & Manvelyan, H. M. (2022) · THE NEW ARMENIAN MEDICAL JOURNAL · doi:10.56936/18290825-2022.16.4-23 · Cited by 1 · see citing works
Involvement of the Cholinergic System in Levodopa-Induced Dyskinesia
Quik, M., Bordia, T., Zhang, D., & Perez, X. A. (2014) · Springer eBooks · doi:10.1007/978-1-4471-6503-3_16
Self-citationKoopman, H. J. M. (2013) · Utrecht University Repository (Utrecht University)
Drenan, R. M., Patzlaff, N. E., & MichaelMcIntosh, J. (2010)
Lambert, C. S. (2015) · Digital Commons - University of South Florida (University of South Florida)
LEVODOPAN AIHEUTTAMIEN DYSKINESIOIDEN NYKYISET JA KEHITTEILLÄ OLEVAT HOITOMUODOT
Nousiainen, S. (2016) · Työväentutkimus Vuosikirja
Arakelyan, N. L., Kesoyan., A. A., Aloyan, D. A., & Manvelyan, H. M. (2023) · MEDICINE SCIENCE AND EDUCATION · doi:10.56936/18291775-2023.36-45
Malekizadeh, Y., Hassankhani, K., Kingslake, A. E., Annett, L. E., Shoaib, M. C., & Iravani, M. M. (2025) · Neuropharmacology · doi:10.1016/j.neuropharm.2025.110786
“A substantial body of preclinical literature demonstrates that pharmacological modulation of nicotinic acetylcholine receptors (nAChRs) can attenuate levodopa-induced dyskinesia (LID).”
Influential
- Authors
- Bordia, T., Campos, C., McIntosh, J. M., & Quik, M.
- Affiliations
- SRI International (US)
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 333
- Issue
- 3
- Pages
- 929-938
- ISSN
- 0022-3565 (ISSN-L)
- PMC
- PMC2879940
- OpenAlex
- W2096898998
- Semantic Scholar
- 33584cc62728599acbd77baaad1eaa78fb672a8a
- Cited by
- 82
- References
- 45
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 4 · 2019: 4 · 2018: 7 · 2017: 5 · 2016: 6 · 2015: 9 · 2014: 9 · 2013: 12 · 2012: 6
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH53631, R01MH053631, R29MH053631)
- National Institute on Drug Abuse (R01DA012242, DA12242)
- National Institute of Neurological Disorders and Stroke (R01NS047162, NS42091, NS47162, R01NS042091)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- levodopa-induced dyskinesia, nicotine, nicotinic acetylcholine receptors, receptor desensitization, mecamylamine, abnormal involuntary movements, Parkinson's disease, 6-hydroxydopamine lesion, alpha4beta2 nAChR, cotinine
- MeSH terms
- Amphetamine, Central Nervous System Stimulants, Animals, Antiparkinson Agents, Autoradiography, Behavior, Animal, Calcium Channel Blockers, Cocaine, Dyskinesia, Drug-Induced, Functional Laterality, Levodopa, Male, Mecamylamine, Nicotine, Pyridines, Receptors, Nicotinic, Stereotyped Behavior, Neostriatum, Rats, Sprague-Dawley, Nicotinic Agonists, Nicotinic Antagonists, Bridged Bicyclo Compounds, Heterocyclic, Conotoxins, Dopamine Plasma Membrane Transport Proteins, Rats
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