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?2* nAChRs on VTA dopamine and GABA neurons separately mediate nicotine aversion and reward.


ABSTRACT: Evidence shows that the neurotransmitter dopamine mediates the rewarding effects of nicotine and other drugs of abuse, while nondopaminergic neural substrates mediate the negative motivational effects. ?2* nicotinic acetylcholine receptors (nAChR) are necessary and sufficient for the experience of both nicotine reward and aversion in an intra-VTA (ventral tegmental area) self-administration paradigm. We selectively reexpressed ?2* nAChRs in VTA dopamine or VTA ?-amino-butyric acid (GABA) neurons in ?2-/- mice to double-dissociate the aversive and rewarding conditioned responses to nicotine in nondependent mice, revealing that ?2* nAChRs on VTA dopamine neurons mediate nicotine's conditioned aversive effects, while ?2* nAChRs on VTA GABA neurons mediate the conditioned rewarding effects in place-conditioning paradigms. These results stand in contrast to a purely dopaminergic reward theory, leading to a better understanding of the neurobiology of nicotine motivation and possibly to improved therapeutic treatments for smoking cessation.

SUBMITTER: Grieder TE 

PROVIDER: S-EPMC6925992 | BioStudies | 2019-01-01

REPOSITORIES: biostudies

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