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Cited by 89Nicotinic Acetylcholine Receptors StudySmoking Behavior and CessationTreatment of Major Depression

Nicotinic Partial Agonists Varenicline and Sazetidine-A Have Differential Effects on Affective Behavior

Open access
Turner, Jill R., Castellano, Laura M., Blendy, Julie A.·2010·The Journal of Pharmacology and Experimental Therapeutics
DOI 10.1124/jpet.110.166280PMC PMC2913767
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Abstract

Clinical and preclinical studies suggest that nicotinic acetylcholine receptors are involved in affective disorders; therefore, the potential therapeutic value of nicotinic partial agonists as treatments of these disorders is of growing interest. This study evaluated the effects of acute and chronic administration of nicotine and the alpha4beta2 nicotinic partial agonists varenicline and sazetidine-A in mouse models of anxiety and depression. Acutely, only nicotine and varenicline had anxiolytic effects in the marble-burying test and in the novelty-induced hypophagia (NIH) test. In contrast, in animal models of antidepressant efficacy, such as the forced swim and the tail suspension test, only acute sazetidine-A had significant antidepressant-like effects. The NIH test provides an anxiety-related measure that is sensitive to the effects of chronic but not acute antidepressant treatment. Chronic nicotine and chronic sazetidine-A treatment were effective in this paradigm, but varenicline was ineffective. These results suggest that the partial agonists varenicline and sazetidine-A may have diverse therapeutic benefits in affective disorders.

AI snapshot

Written from the paper’s full text.

TL;DR

Acute nicotine and varenicline produced anxiolytic-like effects in mouse anxiety tests, whereas acute sazetidine-A produced antidepressant-like effects in the forced swim and tail suspension tests. Chronically, nicotine and sazetidine-A reduced novelty-induced hypophagia, but varenicline did not, suggesting differential therapeutic profiles among nicotinic partial agonists.

Key findings

  • Acute nicotine (0.3 mg/kg) and varenicline (0.1 mg/kg) reduced marble burying and reduced latency to consume food in the novelty-induced hypophagia (NIH) test; acute sazetidine-A (0.1 mg/kg) increased NIH latency, indicating an anxiogenic effect.
  • Acute sazetidine-A (1.0 mg/kg at 10 and 30 min) significantly reduced immobility in both the forced swim test and tail suspension test (p = 0.0001), comparable to desipramine; nicotine and varenicline did not significantly alter immobility in either test.
  • Chronic nicotine (18 mg/kg/day) and chronic sazetidine-A (1.8 mg/kg/day) significantly reduced latency to consume food in the novel NIH environment (p = 0.0001), whereas chronic varenicline (1.8 mg/kg/day) had no significant effect.
  • None of the nicotinic compounds had significant effects in the elevated-zero maze; high doses of nicotine (0.6 mg/kg) and sazetidine-A (0.5 and 1.0 mg/kg) reduced locomotor activity, and varenicline (1.0 mg/kg) increased home-cage activity.

Methods

  • Male 129SvJ;C57BL/6J F1 hybrid mice (6–12 weeks, 25–35 g) were tested after acute intraperitoneal injections or 14-day subcutaneous osmotic minipumps; behavioral assays included elevated-zero maze, locomotor activity, marble-burying, NIH, forced swim, and tail suspension tests.
  • Positive controls were chlordiazepoxide (CDP) for anxiety tests and desipramine (DMI) for antidepressant-like tests; chronic NIH used nicotine, sazetidine-A, varenicline, saline, or DMI, with n = 10/group for NIH and n = 6–14 for other assays.
  • Data were analyzed with one- or two-way ANOVA followed by Bonferroni’s multiple comparison test using GraphPad Prism 5.0.

Limitations

  • The paper states that mechanisms underlying acute and chronic effects of nicotine and other nicotinic drugs in anxiety/depression models are not well characterized, and that further functional studies are needed to clarify the relevance of nAChR activation and desensitization.
  • The paper notes that high doses of nicotine and sazetidine-A produced hypolocomotion, which may confound elevated-zero maze and marble-burying results; varenicline’s FST effects in a prior study varied by mouse strain, and the present study used a different hybrid strain.
  • Evident from the text: only male mice were used, behavioral outcomes are preclinical, and the study does not directly measure receptor-level mechanisms in vivo.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1124/jpet.110.166280

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 53 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Acute sazetidine-A has antidepressant-like effects in FST and TST.

    “In contrast, in animal models of antidepressant efficacy, such as the forced swim and the tail suspension test, only acute sazetidine-A had significant antidepressant-like effects.”
    • Also stated in: § Acute Nicotine and Acute Varenicline, but Not Acute Sazetidine-A, Are Anxiolytic in the NIH Test. · hedged
      “The 1.0 mg/kg dose of sazetidine-A at either the 10-or 30-min time point resulted in reduced immobility, indicating an antidepressant-like response.”
    • Also stated in: § Acute Nicotine and Acute Varenicline, but Not Acute Sazetidine-A, Are Anxiolytic in the NIH Test. · plain
      “sazetidine-A displayed an antidepressant-like response in this paradigm at the 1.0 mg/kg dose.”
    Quote in the paperSubstantial claim
  • Findingown data

    CDP significantly increases time spent in open arms of EZM.

    “CDP, a benzodiazepine with proven efficacy in this paradigm (Ring et al., 2006), significantly increased time spent in the open arms (Fig. 1A), indicative of reduced anxiety.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Nicotine, sazetidine-A, and varenicline do not significantly affect time spent in open arms of elevated-zero maze.

    “In contrast, nicotine, sazetidine-A, and varenicline did not significantly affect time spent in the open arms of the elevated-zero maze (Fig. 1A).”
    Quote in the paperSubstantial claim
  • Findingown data

    DMI reduces immobility in TST.

    “DMI significantly reduced immobility in the TST.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Chronic DMI reduces latency in NIH.

    “chronic treatment with the tricyclic antidepressant DMI resulted in significantly reduced latencies in the NIH test.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 27
  • Classified as probably not a substantial claim. 13

  • May combine two claims.

    Findingown data

    Acute nicotine and varenicline, but not sazetidine-A, produce anxiolytic-like effects in marble-burying and NIH tests in mice.

    “Acutely, only nicotine and varenicline had anxiolytic effects in the marble-burying test and in the novelty-induced hypophagia (NIH) test.”
    • Also stated in: § Acute Nicotine and Acute Varenicline, but Not Acute Sazetidine-A, Are Anxiolytic in the NIH Test. · plain
      “Acute Nicotine and Acute Varenicline, but Not Acute Sazetidine-A, Are Anxiolytic in the NIH Test.”
    • Also stated in: § Acute Nicotine and Acute Varenicline, but Not Acute Sazetidine-A, Are Anxiolytic in the NIH Test. · plain
      “Acute administration of 0.3 mg/kg nicotine, which was anxiolytic in the marble-burying test, had a similar effect in the NIH test by reducing the latency to consume food in the novel environment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Chronic nicotine and chronic sazetidine-A, but not chronic varenicline, reduce latency to consume food in novel environment in NIH test.

    “Chronic nicotine and chronic sazetidine-A treatment were effective in this paradigm, but varenicline was ineffective.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Sazetidine-A 1.0 mg/kg reduces immobility in FST at 10 or 30 min, indicating antidepressant-like response.

    “The 1.0 mg/kg dose of sazetidine-A at either the 10-or 30-min time point resulted in reduced immobility, indicating an antidepressant-like response.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    None of treatments significantly changed feeding latency on home test days 1 or 2 or total food intake on homecage test days.

    “None of the treatments resulted in significant differences in latency to consume the food on home day 1 or 2 (Fig. 3) or in total food consumption on homecage test days (Table 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    At lower doses with no locomotor impairment, mice still spend no more time in the open arm.

    “at lower doses where no impairment in locomotion is observed, animals still do not spend more time in the open arm.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    None of chronic treatments significantly affect latency on home day 1 or 2, food consumption, or mean body weights.

    “None of the treatments resulted in significant differences in latency to consume the food on home day 1 or 2 (Fig. 6) or in food consumption on home cage test days or in mean body weights (Table 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Highest dose nicotine and two highest doses sazetidine-A cause profound hypolocomotion in EZM and homecage.

    “the highest dose of nicotine (0.6 mg/kg) and the two highest doses of sazetidine-A (0.5 and 1.0 mg/kg) resulted in profound hypolocomotion in this test (Fig. 1B) as well as in homecage activity (Fig. 1C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Nicotine and varenicline do not reduce immobility in TST at any dose.

    “neither nicotine nor varenicline reduced immobility in the TST at any of the doses tested (Fig. 5).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Sazetidine-A decreased immobility in both the forced swim test and the tail suspension test.

    “Sazetidine-A decreased immobility in both the FST and the TST, two tests that predict antidepressant efficacy.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The forced swim and tail suspension tests are predictive of antidepressant efficacy.

  • May combine two claims.

    Findingown data

    Chronic nicotine and chronic sazetidine-A both produced antidepressant-like responses in the NIH paradigm.

    “Both nicotine and sazetidine-A were found to have antidepressant-like effects after chronic exposure in the NIH paradigm”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In both the marble-burying and the NIH tests, acute administration of nicotine and varenicline produced significant anxiolytic effects.

    “In both the marble-burying and the NIH tests, acute administration of nicotine and varenicline resulted in significant anxiolytic effects (Figs. 2 and 3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Neither nicotine nor varenicline had significant effects in the forced swim test or the tail suspension test.

    “In contrast, neither nicotine nor varenicline had significant effects in these tests.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    People with depression or anxiety may use nicotine to self-medicate.

    “Depression and anxiety are both highly comorbid with nicotine dependence (Paperwalla et al., 2004), and nicotine use may be an attempt at self-medication in these conditions (Markou et al., 1998).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Markou et al., 1998 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The mechanisms behind acute and chronic actions of nicotine and related drugs in anxiety and depression models remain poorly understood.

    “However, mechanisms underlying acute and chronic effects of nicotine and other nicotinic drugs in models of anxiety and depression are not well characterized (Picciotto et al., 2008).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Picciotto et al., 2008 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In clinical use for smoking cessation, varenicline improves positive mood and cognition.

    “Clinically, varenicline has demonstrated enhancement of both positive affect and cognitive function during smoking cessation (Patterson et al., 2009), and it was recently shown to augment the effects of antidepressants in depressed smokers (Philip et al., 2009).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Patterson et al., 2009 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    At α3β4 receptors varenicline is a weaker partial agonist, while at α7 receptors it is a full agonist.

    “Varenicline (Chantix; Pfizer, Groton, CT) is a potent partial agonist at ␣4␤2 nAChRs, with 40 to 60% of the agonist efficacy of nicotine (Rollema et al., 2007), and it is a less potent partial agonist at ␣3␤4 and a full agonist at ␣7 nAChRs (Mihalak et al., 2006;Rollema et al., 2007Rollema et al., , 2009b)).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Mihalak et al., 2006 source

      Not checked in the free run.

    • cites Rollema et al., 2007 source

      Not checked in the free run.

    • cites Rollema et al., 2009b

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In the FST, acute antidepressants, often with home-cage hypolocomotion, increase activity or lower immobility.

    “In this test, acute administration of an antidepressant, which is often accompanied by hypolocomotion in the home cage, results in increased activity or reduced immobility in the FST (Cryan et al., 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cryan et al., 2005 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In vivo, sazetidine-A acts as an effective pain reliever.

    “A recent in vivo study using sazetidine-A found it to be an effective analgesic (Cucchiaro et al., 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cucchiaro et al., 2008 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The elevated-zero maze is considered less ambiguous for anxiolytic testing than the elevated-plus maze or mirror chamber.

    “The elevated-zero maze is a modification of the elevated-plus maze model of anxiety in rodents and has been found to be a less ambiguous model to study anxiolytic activity compared with elevated-plus maze and mirror chamber (Kulkarni et al., 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kulkarni et al., 2007 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Few animal studies have assessed varenicline's behavioral effects in depression models, and none have tested anxiety.

    “Despite its clinical success in smoking cessation (Nides et al., 2008), there have been a limited number of studies evaluating the behavioral effects of varenicline in animal models of depression (Rollema et al., 2009a) and none examining its effects on anxiety.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rollema et al., 2009a

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The TST assesses changes in escape movements and immobility during an unavoidable stressor.

    “Similar to the FST, the TST measures alterations in escape-oriented movements and immobility when placed in an inescapable stressful situation (Cryan et al., 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cryan et al., 2005 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    In the chronic NIH study, minipump and injection saline controls behaved similarly, so they were pooled.

    “No differences in behavior were observed between minipump and injection saline groups in the chronic NIH test; therefore, these groups were combined for analysis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Varenicline is a potent and selective α4β2 partial agonist.

    “Although varenicline, like cytisine, is a potent and selective ␣4␤2 partial agonist (Rollema et al., 2007)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rollema et al., 2007 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationnone given

    Studying these compounds in 129SvJ; C57BL/6J F1 hybrids adds a new strain to the literature.

    “Our use of 129SvJ; C57BL/6J F1 hybrid mice contributes to the literature in evaluating these compounds in a novel strain.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Cytisine shows antidepressant-like effects in both FST and TST.

    “Cytisine, a nicotinic partial agonist, exhibits antidepressant-like activity in the FST and the TST, two tests sensitive to the effects of antidepressant compounds (Mineur et al., 2007(Mineur et al., , 2009)).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Mineur et al., 2007 source

      Not checked in the free run.

    • cites Mineur et al., 2009 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Varenicline has moderate affinity for other nAChRs and acts as a partial agonist at α3β4 and a full agonist at α7 nAChRs.

    “the high-affinity ␣4␤2 partial agonist varenicline also has moderate affinity for other nAChRs and acts as a partial agonist at ␣3␤4 and a full agonist at ␣7 nAChRs (Mihalak et al., 2006;Rollema et al., 2007).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Mihalak et al., 2006 source

      Not checked in the free run.

    • cites Rollema et al., 2007 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In clinical studies, varenicline administration during smoking cessation improves positive affect and cognitive function.

    “In clinical studies, administration of varenicline during smoking cessation results in the improvement of both positive affect and cognitive function (Patterson et al., 2009).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Patterson 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.

    Study design and conductown data

    FST scores came from ViewPoint tracking and were checked by a trained human scorer.

    “The forced swim score for the entire 6-min test was assessed using the ViewPoint videotracking system (ViewPoint) and confirmed with visual scoring by a trained observer.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    The magnitude of varenicline's effect in the forced swim test varied greatly between C57BL/6J and CD-1 mouse strains, suggesting the effect may be strain specific.

    “However, the magnitude of the effect of varenicline varied greatly in the two mouse strains used in these studies (C57BL/6J and CD-1), suggesting that this effect may be strain specific.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rollema et al., 2009a

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    TST thresholds were set by comparing automated scores against manually scored videos.

    “Optimal thresholds were originally determined by comparing manually scored videotapes with automated scores (Crowley et al., 2006).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Crowley et al., 2006 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Mice were allocated randomly to treatments and tested in a counterbalanced sequence.

    “with animals randomly assigned to treatment conditions and tested in counterbalanced order.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    The dissimilar findings between studies may be due to differences in dosing regime (oral versus minipumps) or differences between the NSF and NIH tests.

    “These dissimilar findings may be due to differences in dosing regime (oral versus minipumps) or differences between the novelty-suppressed feeding paradigm and the novelty-induced hypophagia test.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Sazetidine-A is a rapid desensitizer and would effectively desensitize receptors, which may account for antidepressant-like behaviors observed after an acute dose.

    “whereas sazetidine-A, which is a rapid desensitizer, would effectively desensitize receptors that may account for antidepressant-like behaviors observed in these tests after an acute dose.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Sazetidine-A desensitizes receptors rapidly.

  • May combine two claims.

    Interpretationreasoning

    The desensitization properties of nicotine occur over time, so acute administration may not be sufficient to elicit antidepressant-like responses.

    “Because the desensitization properties of nicotine occur over time, an acute administration may not be sufficient to elicit this response”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Nicotine's desensitization develops gradually.

  • May combine two claims.

    Premisecitation

    The NSF test includes food deprivation, which is itself a stressor and may confound determination of anxiogenic responses to a novel environment.

    “One significant difference between the paradigms is that the NSF test includes food deprivation, which is itself a stressor, and may present a confounding factor in the determination of anxiogenic responses arising from a novel environment (Merali et al., 2003).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Merali et al., 2003 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Sazetidine-A has antidepressant-like activity and utility as a smoking cessation therapy.

    “sazetidine-A, which has antidepressant-like activity and utility as a smoking cessation therapy (Levin et al., 2010)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Levin et al., 2010 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Because these mice are from a genetically diverse background, the results may be more generalizable than results from exclusively inbred strains.

    “In addition, because these mice are from a genetically diverse background, the results from these studies may be more generalizable than results from exclusively inbred strains.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 129SvJ; C57BL/6J F1 hybrid mice have a genetically diverse background.
37 of 37

  • The paper relies on this without support.

    Before this study, sazetidine-A had not been tested in behavioral models of anxiety or depression.

    “However, the activity of sazetidine-A in behavioral models of anxiety or depression has not been investigated.”

  • The paper relies on this without support.

    Chronic nicotinic drug effects in anxiety and depression models remain poorly established.

    “the effects of chronic administration of nicotinic drugs in models of anxiety and depression have not been well established.”

  • The paper relies on this without support.

    The 129SvJ; C57BL/6J F1 hybrid mice have a genetically diverse background.

    “because these mice are from a genetically diverse background”

  • The paper relies on this without support.

    Nicotine's desensitization develops gradually.

    “Because the desensitization properties of nicotine occur over time”

  • The paper relies on this without support.

    Sazetidine-A desensitizes receptors rapidly.

    “sazetidine-A, which is a rapid desensitizer”

  • The paper relies on this without support.

    The forced swim and tail suspension tests are predictive of antidepressant efficacy.

    “two tests that predict antidepressant efficacy”

  • The paper relies on this without support.

    Varenicline is currently the most effective smoking-cessation medication.

    “The most effective medication for smoking cessation currently available is varenicline.”
7 of 7

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?

  • Behavioral testing 10-15 min after infusion is the best time and earliest time point to observe a behavioral effect without drug delivery impacting the anxiety measure.

    “Behavioral testing was carried out 10–15 min after the infusion procedure because previous data with various behavioral assays as well as locomotor studies indicated that this was the best time and the earliest time point to observe a behavioral effect without drug delivery impacting the anxiety measure (Turner et al, 2010).”

    From Divergent Functional Effects of Sazetidine-A and Varenicline During Nicotine Withdrawal (2013) · cites this paper as Turner et al, 2010

  • Chronic treatment with nicotine reduced the latency to feed in a novel environment relative to saline controls.

    “Animals chronically treated with nicotine show a reduced latency to feed in a novel environment relative to saline controls, indicating an anxiolytic response (Figure 1) (Turner et al, 2010).”

    From Divergent Functional Effects of Sazetidine-A and Varenicline During Nicotine Withdrawal (2013) · cites this paper as Turner et al, 2010

  • Previous studies examined the effects of sazetidine-A and varenicline in naïve animals, not nicotine-dependent animals.

    “these previous studies examined the effects of sazetidine-A and varenicline in naı̈ve animals, in not nicotine-dependent animals.”

    From Divergent Functional Effects of Sazetidine-A and Varenicline During Nicotine Withdrawal (2013) · cites this paper as Turner et al, 2010

  • In conflict anxiety paradigms like the NIH test, chronic sazetidine-A has anxiolytic effects, while varenicline does not.

    “in conflict anxiety paradigms like the NIH test, we have previously shown that chronic sazetidine-A has anxiolytic effects, while varenicline does not (Turner et al, 2010).”

    From Divergent Functional Effects of Sazetidine-A and Varenicline During Nicotine Withdrawal (2013) · cites this paper as Turner et al, 2010

  • In preclinical tests, saz-A produces behavior indicative of potential antidepressant and/or antianxiety effects.

    “in preclinical tests saz-A produces behavior indicative of potential antidepressant and/or antianxiety effects (Kozikowski et al., 2009;Turner et al., 2010Turner et al., , 2011;;Caldarone et al., 2011).”

    From Chronic Sazetidine-A at Behaviorally Active Doses Does Not Increase Nicotinic Cholinergic Receptors in Rodent Brain (2012) · cites this paper as Turner 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 sazetidine-A pretreatment times in the tail suspension test

    Major

    The methods specify a 10-minute pretreatment for sazetidine-A in the tail suspension test, but the Figure 5 caption reports a result at both 10 and 30 minutes.

  • Conflicting marble-burying group-size ranges

    Minor

    The methods give a maximum of 10 mice per group for the marble-burying test, whereas the Figure 2 caption gives a maximum of 14.

2 of 2

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Related

Authors
Turner, J. R., Castellano, L. M., & Blendy, J. A.
Affiliations
University of Pennsylvania (US)
ORCID
Venue
The Journal of Pharmacology and Experimental Therapeutics
Publisher
Elsevier BV
Published
2010-08
Volume
334
Issue
2
Pages
665-672
ISSN
0022-3565 (ISSN-L)
DOI
10.1124/jpet.110.166280
PMC
PMC2913767
OpenAlex
W2124166625
Semantic Scholar
1816cbbcb727b143a394c4687fe3be45deab08cb
Cited by
88
References
41
Citations by year
2026: 1 · 2024: 3 · 2023: 5 · 2022: 2 · 2020: 2 · 2019: 3 · 2018: 5 · 2017: 6 · 2016: 7 · 2015: 12 · 2014: 12 · 2013: 7 · 2012: 12
FWCI
4.43
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Pfizer
  • National Institutes of Health (1-F32-)
  • National Institute on Drug Abuse (F32DA026236, 1-F32-DA026236-01A1)
  • National Cancer Institute (CA-143187, P50CA143187)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
nicotinic acetylcholine receptors, varenicline, nicotine, alpha4beta2 nicotinic receptor, anxiolytic effects, antidepressant-like effects, anxiety, depression, mood disorders, novelty-induced hypophagia, forced swim test, tail suspension test, marble burying test, chronic nicotine administration
MeSH terms
Varenicline, Animals, Anxiety, Azetidines, Behavior, Animal, Benzazepines, Chimera, Depression, Male, Nicotine, Pyridines, Quinoxalines, Nicotinic Agonists, Mood Disorders, Mice, Drug Partial Agonism

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-08.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-08.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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