Dopamine signaling through D1-like versus D2-like receptors in the nucleus accumbens core versus shell differentially modulates nicotine reward sensitivity

Considerable evidence implicates the mesolimbic dopamine ( DA) system in the processing of nicotine's reinforcing properties, specifically the ventral tegmental area ( VTA) and the terminal fields of VTA DAergic projections to the core ( NAcore) and shell ( NAshell) subdivisions of the nucleus accumbens ( NAc). However, the specific roles of DA D1- like and D2- like receptor subtypes in nicotine reward processing within these NAc subregions have not been elucidated. We report that microinfusions of DA D1- like or D2- like receptorspecific antagonists into NAcore or NAshell double dissociate the rewarding and aversive properties of systemic or intra- VTA nicotine, and differentially regulate sensitivity to the rewarding properties as well as the motivational valence of either intra- VTA or systemic nicotine administration. Using a place conditioning procedure, NAshell infusions of a D2- like receptor antagonist switched the motivational valence of intra- VTA nicotine from aversive to rewarding and potentiated nicotine reward sensitivity to sub- reward threshold intra- VTA nicotine doses. In contrast, NAcore infusions of aD1- like receptor antagonist switched intra- VTA nicotine aversion to reward, and potentiated reward sensitivity to sub- reward threshold nicotine doses. Thus, D1- like versus D2- like receptors in NAcore versus NAshell subdivisions play functionally dissociable roles in modulating systemic or intra- VTA nicotine motivational processing.