{"id":123669,"date":"2020-07-23T19:46:56","date_gmt":"2020-07-23T17:46:56","guid":{"rendered":"https:\/\/www.bordeaux-neurocampus.fr\/?p=123669"},"modified":"2020-07-23T19:46:56","modified_gmt":"2020-07-23T17:46:56","slug":"vincent-david-et-al-in-journal-of-neuroscience","status":"publish","type":"post","link":"https:\/\/www.bordeaux-neurocampus.fr\/en\/vincent-david-et-al-in-journal-of-neuroscience\/","title":{"rendered":"Vincent David et al in Journal of Neuroscience<\/em>"},"content":{"rendered":"

Nicotine addiction, through smoking, is the principal cause of preventable mortality worldwide. Human genome-wide association studies have linked polymorphisms in the CHRNA5-CHRNA3-CHRNB4 gene cluster, coding for the a5, a3, and b4 nicotinic acetylcholine receptor (nAChR) subunits, to nicotine addiction. b4*nAChRs have been implicated in nicotine withdrawal, aversion, and reinforcement. Here we show that b4*nAChRs also are involved in non-nicotine mediated responses that may predispose to addiction-related behaviors. b4 knock-out (KO) male mice show increased novelty-induced locomotor activity, lower baseline anxiety, and motivational deficits in operant conditioning for palatable food rewards and in reward-based Go\/No-go tasks. To further explore reward deficits we used intracranial self-administration (ICSA) by injecting nicotine directly into the ventral tegmental area (VTA) in mice. We found that, at low nicotine doses, b4KO self-administer less than wild-type (WT) mice. Conversely, at high nicotine doses, this was reversed and b4KO self-administered more than WT mice, whereas b4-overexpressing mice avoided nicotine injections. Viral expression of b4 subunits in medial habenula (MHb), interpeduncular nucleus (IPN), and VTA of b4KO mice revealed dose- and region- dependent differences: b4*nAChRs in the VTA potentiated nicotine-mediated rewarding effects at all doses, whereas b4*nAChRs in the MHb-IPN pathway limited VTA-ICSA at high nicotine doses. Together, our findings indicate that the lack of functional b4*nAChRs result in deficits in reward sensitivity including increased ICSA at high doses of nicotine. Normal, WT levels of nicotine ICSA are restored by re-expression of b4*nAChRs in the MHb-IPN. These data indicate that the b4 subunit is a critical modulator of reward-related behaviors, and that \u03b24*nAChRs may provide a promising novel drug target for smoking cessation.<\/p>\n

\"\"<\/a>
Intra-VTA self-administration of high nicotine doses in \u03b24-\/-; \u03b24+\/+; \u03b24 overexpressing (TABAC) mice, and \u03b24-\/- re-expressing the \u03b24 subunit in the VTA, IPN or MHb through lentivirus-induced vectorization. Whereas WT mice displayed a weak preference or express an alternation behavior, \u03b24-\/- develop strong nicotine self-administration. In sharp contrast, TABAC mice avoided nicotine injections. The level of nicotine intake thus is inversely correlated to the number of \u03b24 receptors. Re-expression of the \u03b24 subunit in the MHb or IPN restored limitation of nicotine intake close to WT levels.<\/figcaption><\/figure>\n

Reference<\/h2>\n

Husson M<\/strong>, Harrington L, Tochon L<\/strong>, Cho Y<\/strong>, Iba\u00f1ez-Tallon I, Maskos U, David V<\/strong>.
\n\u03b24-Nicotinic Receptors Are Critically Involved in Reward-Related Behaviors and Self-Regulation of Nicotine Reinforcement.<\/a>
\nJ Neurosci. 2020 Apr 22;40(17):3465-3477.
\ndoi: 10.1523\/JNEUROSCI.0356-19.2020<\/a>.<\/p>\n

F1000 recommendation<\/h4>\n

This article was recently awarded with a F1000 recommendation for exceptional importance:
\nRead the F1000 recommendation for this paper here.<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

\u03b24-Nicotinic Receptors Are Critically Involved in Reward-Related Behaviors and Self-Regulation of Nicotine Reinforcement.<\/p>\n","protected":false},"author":108,"featured_media":123706,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[71],"tags":[],"class_list":["post-123669","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-highlight-en"],"_links":{"self":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts\/123669","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/users\/108"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/comments?post=123669"}],"version-history":[{"count":0,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/posts\/123669\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/media\/123706"}],"wp:attachment":[{"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/media?parent=123669"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/categories?post=123669"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bordeaux-neurocampus.fr\/en\/wp-json\/wp\/v2\/tags?post=123669"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}