尼古丁
药理学
内侧前脑束
光遗传学
刺激
化学
被盖腹侧区
神经科学
内科学
内分泌学
医学
多巴胺
生物
多巴胺能
作者
Luis M. Tuesta,Zuxin Chen,Alexander Duncan,Christie D. Fowler,Masago Ishikawa,Brian Lee,Xinan Liu,Qun Lu,Michael D. Cameron,Matthew R. Hayes,Theodore M. Kamenecka,Matthew Pletcher,Paul J. Kenny
摘要
Tobacco smokers titrate their nicotine intake to avoid its noxious effects, sensitivity to which may influence vulnerability to tobacco dependence, yet mechanisms of nicotine avoidance are poorly understood. Here we show that nicotine activates glucagon-like peptide-1 (GLP-1) neurons in the nucleus tractus solitarius (NTS). The antidiabetic drugs sitagliptin and exenatide, which inhibit GLP-1 breakdown and stimulate GLP-1 receptors, respectively, decreased nicotine intake in mice. Chemogenetic activation of GLP-1 neurons in NTS similarly decreased nicotine intake. Conversely, Glp1r knockout mice consumed greater quantities of nicotine than wild-type mice. Using optogenetic stimulation, we show that GLP-1 excites medial habenular (MHb) projections to the interpeduncular nucleus (IPN). Activation of GLP-1 receptors in the MHb-IPN circuit abolished nicotine reward and decreased nicotine intake, whereas their knockdown or pharmacological blockade increased intake. GLP-1 neurons may therefore serve as 'satiety sensors' for nicotine that stimulate habenular systems to promote nicotine avoidance before its aversive effects are encountered.
科研通智能强力驱动
Strongly Powered by AbleSci AI