| First Author | Grieder TE | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 51 | Pages | 25968-25973 |
| PubMed ID | 31776253 | Mgi Jnum | J:282796 |
| Mgi Id | MGI:6383306 | Doi | 10.1073/pnas.1908724116 |
| Citation | Grieder TE, et al. (2019) beta2* nAChRs on VTA dopamine and GABA neurons separately mediate nicotine aversion and reward. Proc Natl Acad Sci U S A 116(51):25968-25973 |
| abstractText | 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. beta2* 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 beta2* nAChRs in VTA dopamine or VTA gamma-amino-butyric acid (GABA) neurons in beta2(-/-) mice to double-dissociate the aversive and rewarding conditioned responses to nicotine in nondependent mice, revealing that beta2* nAChRs on VTA dopamine neurons mediate nicotine's conditioned aversive effects, while beta2* 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. |
