Altered nicotine reward-associated behavior following ?4 nAChR subunit deletion in ventral midbrain.

ABSTRACT: Nicotinic acetylcholine receptors containing ?4 subunits (?4?2* nAChRs) are critical for nicotinic cholinergic transmission and the addictive action of nicotine. To identify specific activities of these receptors in the adult mouse brain, we coupled targeted deletion of ?4 nAChR subunits with behavioral and and electrophysiological measures of nicotine sensitivity. A viral-mediated Cre/lox approach allowed us to delete ?4 from ventral midbrain (vMB) neurons. We used two behavioral assays commonly used to assess the motivational effects of drugs of abuse: home-cage oral self-administration, and place conditioning. Mice lacking ?4 subunits in vMB consumed significantly more nicotine at the highest offered nicotine concentration (200 ?g/mL) compared to control mice. Deletion of ?4 subunits in vMB blocked nicotine-induced conditioned place preference (CPP) without affecting locomotor activity. Acetylcholine-evoked currents as well as nicotine-mediated increases in synaptic potentiation were reduced in mice lacking ?4 in vMB. Immunostaining verified that ?4 subunits were deleted from both dopamine and non-dopamine neurons in the ventral tegmental area (VTA). These results reveal that attenuation of ?4* nAChR function in reward-related brain circuitry of adult animals may increase nicotine intake by enhancing the rewarding effects and/or reducing the aversive effects of nicotine.

SUBMITTER: Peng C 

PROVIDER: S-EPMC5536316 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature