title: Rewarding and aversive effects of nicotine are segregated within the nucleus accumbens.
abstract: Forebrain dopamine plays a critical role in motivated behavior. According to the classic view, mesolimbic dopamine selectively guides behavior motivated by positive reinforcers. However, this has been challenged in favor of a wider role encompassing aversively motivated behavior. This controversy is particularly striking in the case of nicotine, with opposing claims that either the rewarding or the aversive effect of nicotine is critically dependent on mesolimbic dopamine transmission. In the present study, the effects of 6-hydroxydopamine lesions of nucleus accumbens core vs. medial shell on intravenous nicotine conditioned place preference and conditioned taste aversion were examined in male adult rats. Dopaminergic denervation in accumbens medial shell was associated with decreased nicotine conditioned place preference. Conversely, denervation in accumbens core was associated with an increase in conditioned place preference. In addition, dopaminergic denervation of accumbens core but not medial shell abolished conditioned taste aversion for nicotine. We conclude that nucleus accumbens core and medial shell dopaminergic innervation exert segregated effects on rewarding and aversive effects of nicotine. More generally, our findings indicate that dopaminergic transmission may mediate or enable opposing motivational processes within functionally distinct domains of the accumbens.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.
authors.forename: Laurie H L
authors.initials: LH
authors.lastname: Sellings
authors.forename: Golriz
authors.initials: G
authors.lastname: Baharnouri
authors.forename: Lindsey E
authors.initials: LE
authors.lastname: McQuade
authors.forename: Paul B S
authors.initials: PB
authors.lastname: Clarke
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D002755:Choice Behavior / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012201:Reward; D013037:Spatial Behavior / Q000187:drug effects; D009435:Synaptic Transmission / Q000502:physiology*; D013649:Taste / Q000502:physiology
chemical_list: D009538:Nicotine; D016627:Oxidopamine; D004298:Dopamine