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  • 标题:β2* nAChRs on VTA dopamine and GABA neurons separately mediate nicotine aversion and reward
  • 本地全文:下载
  • 作者:Taryn E. Grieder ; Morgane Besson ; Geith Maal-Bared
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2019
  • 卷号:116
  • 期号:51
  • 页码:25968-25973
  • DOI:10.1073/pnas.1908724116
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要: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. β2* 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 β2* nAChRs in VTA dopamine or VTA γ-amino-butyric acid (GABA) neurons in β2 −/− mice to double-dissociate the aversive and rewarding conditioned responses to nicotine in nondependent mice, revealing that β2* nAChRs on VTA dopamine neurons mediate nicotine’s conditioned aversive effects, while β2* 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..
  • 关键词:nicotinic receptors ; place;conditioning ; nicotine motivation ; reward ; aversion
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