title: Varenicline decreases ethanol intake and increases dopamine release via neuronal nicotinic acetylcholine receptors in the nucleus accumbens.
abstract: OBJECTIVE
  Varenicline, a neuronal nicotinic acetylcholine receptor (nAChR) modulator, decreases ethanol consumption in rodents and humans. The proposed mechanism of action for varenicline to reduce ethanol consumption has been through modulation of dopamine (DA) release in the nucleus accumbens (NAc) via α4*-containing nAChRs in the ventral tegmental area (VTA). However, presynaptic nAChRs on dopaminergic terminals in the NAc have been shown to directly modulate dopaminergic signalling independently of neuronal activity from the VTA. In this study, we determined whether nAChRs in the NAc play a role in varenicline's effects on ethanol consumption.
  
  
  METHODS
  Rats were trained to consume ethanol using the intermittent-access two-bottle choice protocol for 10 weeks. Ethanol intake was measured after varenicline or vehicle was microinfused into the NAc (core, shell or core-shell border) or the VTA (anterior or posterior). The effect of varenicline treatment on DA release in the NAc was measured using both in vivo microdialysis and in vitro fast-scan cyclic voltammetry (FSCV).
  
  
  RESULTS
  Microinfusion of varenicline into the NAc core and core-shell border, but not into the NAc shell or VTA, reduced ethanol intake following long-term ethanol consumption. During microdialysis, a significant enhancement in accumbal DA release occurred following systemic administration of varenicline and FSCV showed that varenicline also altered the evoked release of DA in the NAc.
  
  
  CONCLUSIONS
  Following long-term ethanol consumption, varenicline in the NAc reduces ethanol intake, suggesting that presynaptic nAChRs in the NAc are important for mediating varenicline's effects on ethanol consumption.
authors.affiliation: Ernest Gallo Clinic and Research Center, University of California San Francisco, Emeryville, CA, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Feduccia
authors.forename: J A
authors.initials: JA
authors.lastname: Simms
authors.forename: D
authors.initials: D
authors.lastname: Mill
authors.forename: H Y
authors.initials: HY
authors.lastname: Yi
authors.forename: S E
authors.initials: SE
authors.lastname: Bartlett
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D008297:Male; D008845:Microinjections; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013329:Structure-Activity Relationship; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D011810:Quinoxalines; D011978:Receptors, Nicotinic; D000431:Ethanol; D004298:Dopamine; D000068580:Varenicline
keywords: alcohol; dopamine; ethanol; fast-scan cyclic voltammetry; in vivo microdialysis; microinfusion; nicotinic acetylcholine receptors (nAChRs); varenicline