Varenicline as a smoking cessation aid in schizophrenia: effects on smoking behavior and reward sensitivity

Dutra, Sunny J.; Stoeckel, Luke E.; Carlini, Sara V.; Pizzagalli, Diego A.; Evins, A. Eden

doi:10.1007/s00213-011-2373-6

Cited by 38 publications

(24 citation statements)

References 67 publications

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“…A recent study found that maintenance therapy with varenicline prolonged tobacco abstinence rates in patients with schizophrenia (Evins et al, 2014). Moreover, schizophrenia patients with lower baseline symptoms of affective flattening were more likely to achieve smoking abstinence and demonstrated larger increases in reward sensitivity during varenicline treatment (Dutra et al, 2012). Table 3 depicts the results of clinical trials of nAChR agonists and PAMs in patients with schizophrenia.…”

Section: Resultsmentioning

confidence: 99%

nAChR dysfunction as a common substrate for schizophrenia and comorbid nicotine addiction: Current trends and perspectives

Parikh

Kutlu

Gould

2016

Schizophrenia Research

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Introduction The prevalence of tobacco use in the population with schizophrenia is enormously high. Moreover, nicotine dependence is found to be associated with symptom severity and poor outcome in patients with schizophrenia. The neurobiological mechanisms that explain schizophrenia-nicotine dependence comorbidity are not known. This study systematically reviews the evidence highlighting the contribution of nicotinic acetylcholine receptors (nAChRs) to nicotine abuse in schizophrenia. Methods Electronic data bases (Medline, Google Scholar, and Web of Science) were searched using the selected key words that match the aims set forth for this review. A total of 275 articles were used for the qualitative synthesis of this review. Results Substantial evidence from preclinical and clinical studies indicated that dysregulation of α7 and β2-subunit containing nAChRs account for the cognitive and affective symptoms of schizophrenia and nicotine use may represent a strategy to remediate these symptoms. Additionally, recent meta-analyses proposed that early tobacco use may itself increase the risk of developing schizophrenia. Genetic studies demonstrating that nAChR dysfunction that may act as a shared vulnerability factor for comorbid tobacco dependence and schizophrenia were found to support this view. The development of nAChR modulators was considered an effective therapeutic strategy to ameliorate psychiatric symptoms and to promote smoking cessation in schizophrenia patients. Conclusions The relationship between schizophrenia and smoking is complex. While the debate for the self-medication versus addiction vulnerability hypothesis continues, it is widely accepted that a dysfunction in the central nAChRs represent a common substrate for various symptoms of schizophrenia and comorbid nicotine dependence.

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Section: Resultsmentioning

confidence: 99%

nAChR dysfunction as a common substrate for schizophrenia and comorbid nicotine addiction: Current trends and perspectives

Parikh

Kutlu

Gould

2016

Schizophrenia Research

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“…Numerous studies indicate that varenicline potently and selectively interacts at ␣4␤2* nAChRs (Mihalak et al, 2006;Rollema et al, 2007;Reperant et al, 2010;Brandon et al, 2011;Maloku et al, 2011;Dutra et al, 2012;Lotfipour et al, 2012;Shim et al, 2012). In fact, it has been suggested that varenicline exerts its beneficial effects as a smoking cessation aid by targeting this nAChR population.…”

Section: Discussionmentioning

confidence: 99%

Varenicline Is a Potent Partial Agonist at α6β2* Nicotinic Acetylcholine Receptors in Rat and Monkey Striatum

Bordia

Hrachova

Chin

et al. 2012

J Pharmacol Exp Ther

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Extensive evidence indicates that varenicline reduces nicotine craving and withdrawal symptoms by modulating dopaminergic function at ␣4␤2* nicotinic acetylcholine receptors (nAChRs) (the asterisk indicates the possible presence of other nicotinic subunits in the receptor complex). More recent data suggest that ␣6␤2* nAChRs also regulate dopamine release and mediate nicotine reinforcement. The present experiments were therefore done to test the effect of varenicline on ␣6␤2* nAChRs and their function, because its interaction with this subtype is currently unclear. Receptor competition studies showed that varenicline inhibited ␣6␤2* nAChR binding (K i ϭ 0.12 nM) as potently as ␣4␤2* nAChR binding (K i ϭ 0.14 nM) in rat striatal sections and with ϳ20-fold greater affinity than nicotine. Functionally, varenicline was more potent in stimulating ␣6␤2* versus ␣4␤2* nAChR-mediated [3 H]dopamine release from rat striatal synaptosomes with EC 50 values of 0.007 and 0.086 M, respectively. However, it acted as a partial agonist on ␣6␤2* and ␣4␤2* nAChR-mediated [ 3 H]dopamine release with maximal efficacies of 49 and 24%, respectively, compared with nicotine. We also evaluated varenicline's action in striatum of monkeys, a useful animal model for comparison with humans. Varenicline again potently inhibited monkey striatal ␣6␤2* (K i ϭ 0.13 nM) and ␣4␤2* (K i ϭ 0.19 nM) nAChRs in competition studies. Functionally, it potently stimulated both ␣6␤2* (EC 50 ϭ 0.014 M) and ␣4␤2* (EC 50 ϭ 0.029 M) nAChR-mediated [ 3 H]dopamine release from monkey striatal synaptosomes, again acting as a partial agonist relative to nicotine at both subtypes. These data suggest that the ability of varenicline to interact at ␣6␤2* nAChRs may contribute to its efficacy as a smoking cessation aid.

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“…Although smoking cessation is clearly an option, most smoking cessation programs yield only a 12–15% abstinence rate at 1 year [32,33,34]. In fact, the common smoking cessation treatment, varenicline (trade name: Chantix), has been shown to exacerbate psychotic symptoms [35], although this may be related to severity of negative symptoms in that particular individual [36], and other studies have shown that varenicline may actually be efficacious for smoking cessation in schizophrenia [37,38]. …”

Section: Schizophrenia and Tobacco Dependencementioning

confidence: 99%

Schizophrenia and Substance Abuse Comorbidity: Nicotine Addiction and the Neonatal Quinpirole Model

Brown¹,

Maple²,

Perna³

et al. 2012

Dev Neurosci

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This review focuses on nicotine comorbidity in schizophrenia, and the insight into this problem provided by rodent models of schizophrenia. A particular focus is on age differences in the response to nicotine, and how this relates to the development of the disease and difficulties in treatment. Schizophrenia is a particularly difficult disease to model in rodents due to the fact that it has a plethora of symptoms ranging from paranoia and delusions of grandeur to anhedonia and negative affect. The basis of these symptoms is believed to be due to neurochemical abnormalities and neuropathology in the brain, which most models have attempted to emulate. A brief review of findings regarding nicotine use and abuse in schizophrenics is presented, with findings using rodent models that have been able to provide insight into the mechanisms of addiction. A common clinical approach to the treatment of nicotine addiction in the schizophrenic population has been that these drugs are used for self-medication purposes, and it is clear that self-medication may actually be directed at several symptoms, including cognitive impairment and anhedonia. Finally, our laboratory has reported across a series of studies that neonatal treatment with the dopamine D₂/D₃ receptor agonist quinpirole results in long-term increases in dopamine-like receptor sensitivity, consistent with data reporting increases in dopamine D₂ receptor function in schizophrenia. Across these studies, we have reported several behavioral, neurochemical, and genetic consistencies with the disease, and present a hypothesis for what we believe to be the basis of psychostimulant addiction in schizophrenia.

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Varenicline as a smoking cessation aid in schizophrenia: effects on smoking behavior and reward sensitivity

Cited by 38 publications

References 67 publications

nAChR dysfunction as a common substrate for schizophrenia and comorbid nicotine addiction: Current trends and perspectives

nAChR dysfunction as a common substrate for schizophrenia and comorbid nicotine addiction: Current trends and perspectives

Varenicline Is a Potent Partial Agonist at α6β2* Nicotinic Acetylcholine Receptors in Rat and Monkey Striatum

Schizophrenia and Substance Abuse Comorbidity: Nicotine Addiction and the Neonatal Quinpirole Model

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