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Varenicline Attenuates Relapse‐like Ethanol Drinking Behavior in Mice
Author(s) -
Sajja Ravi Kiran,
Rahman Shafiqur
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.660.2
Subject(s) - varenicline , ethanol , pharmacology , chemistry , nicotinic agonist , partial agonist , saline , agonist , endocrinology , medicine , nicotine , receptor , biochemistry
Nicotinic acetylcholine receptors (nAChRs) have been implicated in ethanol drinking behaviors. We have shown that nAChR ligands reduce binge‐like ethanol drinking and preference in mice. Here, we examined the effects of varenicline, a high affinity α4β2* nAChR partial agonist, on ethanol deprivation effect (EDE), a model for relapse‐like ethanol drinking in C57BL/6J mice. After habituation to 15% (v/v) ethanol drinking using a 24 h two‐bottle choice procedure, mice were exposed to repeated cycles of ethanol deprivation (5 day) and re‐exposure (2 day). Following 3 rd deprivation cycle, animals received repeated intraperitoneal injections of saline (control) or varenicline (0.5 or 3.0 mg/kg), starting at 12 h prior to ethanol re‐exposure. Control mice exhibited a significant increase in ethanol intake (% baseline) during 3 rd re‐exposure (150% at 4 h and 155% at 24 h access). Varenicline (0.5 or 3.0 mg/kg) significantly decreased ethanol intake (% control) at post 4 h (50% or 66% respectively) and 24 h (33% or 50% respectively). In addition, varenicline (3 mg/kg) suppressed locomotor activity in mice compared to control. Effects of varenicline on ethanol clearance and chronic ethanol‐induced ΔFosB expression are being studied. Overall, the study indicates that varenicline attenuates EDE in mice by targeting α4β2* nAChRs and suggests an important role of nAChRs in relapse‐like ethanol drinking behaviors. (Supported in part by SDSURF‐JRF grant)