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Parallel anxiolytic-like effects and upregulation of neuronal nicotinic acetylcholine receptors following chronic nicotine and varenicline

, : Parallel anxiolytic-like effects and upregulation of neuronal nicotinic acetylcholine receptors following chronic nicotine and varenicline. Nicotine & Tobacco Research 13(1): 41-46

Clinical and preclinical studies suggest that regulation of nicotinic acetylcholine receptors (nAChR) maybe involved in the etiology of withdrawal symptoms. We evaluated heteromeric nAChR regulation via [³H]epibatidine binding following cessation of chronic nicotine or varenicline treatment. Animals were concurrently tested in the marble-burying test to evaluate treatment-related effects. We found that both nicotine (18 mg/kg/day, free base) and varenicline (1.8 mg/kg/day) chronically administered for 14 days upregulated nAChRs significantly in the cortex, hippocampus, striatum, and thalamus. The duration of upregulation (up to 72 hr) was both drug and region specific. In addition to nAChR upregulation, chronic administration of both nicotine and varenicline had anxiolytic-like effects in the marble-burying test. This effect was maintained for 48 hr following cessation of varenicline but was absent 24 hr following cessation from nicotine. Additionally, marble-burying behavior positively correlated to the regulation of cortical nAChRs following cessation of either treatment. Varenicline has been shown to be an efficacious smoking cessation aid, with a proposed mechanism of action that includes modulation of dopamine release in reward areas of the brain. Our studies show that varenicline elicits both anxiolytic effects in the marble-burying test as well as region- and time-specific receptor upregulation. These findings suggest receptor upregulation as a mechanism for its efficacy as a smoking cessation therapy.


PMID: 21097981

DOI: 10.1093/ntr/ntq206

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