Continuous and intermittent nicotine treatment reduces l-3,4-dihydroxyphenylalanine (l-DOPA)-induced dyskinesias in a rat model of Parkinson's disease
Abstract
The development of abnormal involuntary movements (AIMs) or dyskinesias is a serious complication of L-DOPA [L-3,4-dihydroxyphenylalanine] therapy for Parkinson's disease. Our previous work had shown that intermittent nicotine dosing reduced L-DOPA-induced dyskinetic-like movements in nonhuman primates. A readily available nicotine formulation is the nicotine patch, which provides a constant source of nicotine. However, constant nicotine administration more readily desensitizes nicotinic receptors, to possibly yield alternate behavioral outcomes. Therefore, we investigated whether constant nicotine administration reduced L-DOPA-induced AIMs in a rat parkinsonian model, with results compared with those with intermittent nicotine dosing. Rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion were exposed to either intermittent (drinking water) or constant (minipump) nicotine for > or = 2 weeks at doses that yielded plasma levels of the nicotine metabolite cotinine similar to those in smokers. The rats were next treated with L-DOPA/benserazide (8 or 12 mg/kg/15 mg/kg) for > or = 3 weeks to allow for the development of AIMs, with nicotine treatment continued. Both modes of nicotine administration resulted in > or = 50% decline in L-DOPA-induced AIMs. Nicotine treatment also significantly reduced AIMs in L-DOPA-primed rats using either dosing regimen, whereas nicotine removal led to an increase in AIMs. There was no effect of nicotine on various measures of motor performance in 6-OHDA-lesioned rats. In summary, nicotine provided either via the drinking water or minipump reduced L-DOPA-induced AIMs in a rat model of Parkinson's disease. These results suggest that either intermittent or constant nicotine treatment may be useful in the treatment of L-DOPA-induced dyskinesias in patients with Parkinson's disease.
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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).”
From Nicotinic receptor-mediated reduction in l-DOPA-induced dyskinesias may occur via desensitization (2010) · cites this paper as Bordia et al., 2008
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.”
From Nicotinic receptor-mediated reduction in l-DOPA-induced dyskinesias may occur via desensitization (2010) · cites this paper as Bordia et al., 2008
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).”
From Nicotinic receptor-mediated reduction in l-DOPA-induced dyskinesias may occur via desensitization (2010) · cites this paper as Bordia et al., 2008
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).”
From Nicotinic receptor-mediated reduction in l-DOPA-induced dyskinesias may occur via desensitization (2010) · cites this paper as Bordia et al., 2008
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.”
From Nicotinic receptor-mediated reduction in l-DOPA-induced dyskinesias may occur via desensitization (2010) · cites this paper as Bordia et al., 2008
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).”
From Nicotinic receptor-mediated reduction in l-DOPA-induced dyskinesias may occur via desensitization (2010) · cites this paper as Bordia et al., 2008
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References 45 · Cited by 120
- Authors
- Bordia, T., Campos, C., Huang, L., & Quik, M.
- Affiliations
- Parkinson's Institute and Clinical Center (US)
- ORCID
- Bordia, Tanuja
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 327
- Issue
- 1
- Pages
- 239-247
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2161336661
- Semantic Scholar
- 9940f3069715dbd3d18374d8303bcf0240d7afdc
- Cited by
- 120
- References
- 45
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 7 · 2018: 8 · 2017: 8 · 2016: 4 · 2015: 16 · 2014: 9 · 2013: 16 · 2012: 10
- FWCI
- 5.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS047162, NS42091, R01NS034886, NS47162, R01NS042091)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- nicotine, levodopa-induced dyskinesia, abnormal involuntary movements, Parkinson's disease, 6-hydroxydopamine lesion, nicotine patch, nicotinic receptor desensitization, rat model
- MeSH terms
- Animals, Corpus Striatum, Disease Models, Animal, Dyskinesia, Drug-Induced, Infusion Pumps, Levodopa, Male, Nicotine, Parkinson Disease, Rats, Sprague-Dawley, Dopamine Plasma Membrane Transport Proteins, Rats
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