{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:48:56Z","timestamp":1787014136479,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,9,6]],"date-time":"2018-09-06T00:00:00Z","timestamp":1536192000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["863.15.012"],"award-info":[{"award-number":["863.15.012"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000874","name":"Brain and Behavior Research Foundation","doi-asserted-by":"publisher","award":["25190"],"award-info":[{"award-number":["25190"]}],"id":[{"id":"10.13039\/100000874","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["335333"],"award-info":[{"award-number":["335333"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006390","name":"Universit\u00e9 de Lausanne","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006390","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2019,8]]},"abstract":"Abstract<\/jats:title>\n \n Lateral habenula (\n LH<\/jats:styled-content>\n b) hyperactivity plays a pivotal role in the emergence of negative emotional states, including those occurring during withdrawal from addictive drugs. We have previously implicated cocaine\u2010driven adaptations at synapses from the entopeduncular nucleus (\n EPN<\/jats:styled-content>\n ) to the\n LH<\/jats:styled-content>\n b in this process. Specifically, ionotropic\n \n GABA\n A<\/jats:sub>\n <\/jats:styled-content>\n receptor (R)\u2010mediated neurotransmission at\n EPN<\/jats:styled-content>\n \u2010to\u2010\n LH<\/jats:styled-content>\n b synapses is reduced during cocaine withdrawal, due to impaired vesicle filling. Recent studies have shown that metabotropic\n \n GABA\n B<\/jats:sub>\n R\n <\/jats:styled-content>\n signaling also controls\n LH<\/jats:styled-content>\n b activity, although its role at\n EPN<\/jats:styled-content>\n \u2010to\u2010\n LH<\/jats:styled-content>\n b synapses during drug withdrawal is unknown. Here, we predicted that cocaine treatment would reduce\n \n GABA\n B<\/jats:sub>\n R\n <\/jats:styled-content>\n \u2010mediated neurotransmission at\n EPN<\/jats:styled-content>\n \u2010to\u2010\n LH<\/jats:styled-content>\n b synapses. We chronically treated mice with saline or cocaine, prepared brain slices after two days of withdrawal and performed voltage\u2010clamp recordings from\n LH<\/jats:styled-content>\n b neurons whilst optogenetically stimulating\n EPN<\/jats:styled-content>\n terminals. Compared with controls, mice in cocaine withdrawal exhibited reduced\n \n GABA\n A<\/jats:sub>\n R\n <\/jats:styled-content>\n \u2010mediated input to\n LH<\/jats:styled-content>\n b neurons, and a reduced occurrence of\n \n GABA\n B<\/jats:sub>\n R\n <\/jats:styled-content>\n \u2010signaling at\n EPN<\/jats:styled-content>\n \u2010to\u2010\n LH<\/jats:styled-content>\n b synapses. We then assessed the underlying mechanism of this decrease. Application of\n \n GABA\n B<\/jats:sub>\n R\n <\/jats:styled-content>\n agonist baclofen evoked similar postsynaptic responses in\n EPN<\/jats:styled-content>\n \u2010innervated\n LH<\/jats:styled-content>\n b neurons in saline\u2010 and cocaine\u2010treated mice. Release probability at\n EPN<\/jats:styled-content>\n \u2010to\u2010\n LH<\/jats:styled-content>\n b\n GABA<\/jats:styled-content>\n ergic synapses was also comparable between groups. However, incubating brain slices in glutamine to facilitate\n GABA<\/jats:styled-content>\n vesicle filling, normalized\n \n GABA\n B<\/jats:sub>\n R\n <\/jats:styled-content>\n \u2010currents at\n EPN<\/jats:styled-content>\n \u2010to\u2010\n LH<\/jats:styled-content>\n b synapses in cocaine\u2010treated mice. Overall, we show that during cocaine withdrawal, together with reduced\n \n GABA\n A<\/jats:sub>\n R\n <\/jats:styled-content>\n transmission, also\n \n GABA\n B<\/jats:sub>\n R\n <\/jats:styled-content>\n \u2010mediated inhibitory signaling is diminished at\n EPN<\/jats:styled-content>\n \u2010to\u2010\n LH<\/jats:styled-content>\n b synapses, likely via the same presynaptic deficit. In concert, these alterations are predicted to contribute to the emergence of drug withdrawal symptoms, facilitating drug relapse.\n <\/jats:p>","DOI":"10.1111\/ejn.14120","type":"journal-article","created":{"date-parts":[[2018,8,17]],"date-time":"2018-08-17T16:24:24Z","timestamp":1534523064000},"page":"2124-2133","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Cocaine withdrawal reduces GABA\n B<\/sub>\n R transmission at entopeduncular nucleus \u2013 lateral habenula synapses"],"prefix":"10.1111","volume":"50","author":[{"given":"Dorine","family":"Tan","sequence":"first","affiliation":[{"name":"Institut du Fer \u00e0 Moulin Paris France"},{"name":"Inserm, UMR\u2010S 839 Paris France"},{"name":"UPMC 75005 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Nuno\u2010Perez","sequence":"additional","affiliation":[{"name":"Department of Fundamental Neurosciences The University of Lausanne Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Mameli","sequence":"additional","affiliation":[{"name":"Institut du Fer \u00e0 Moulin Paris France"},{"name":"Inserm, UMR\u2010S 839 Paris France"},{"name":"UPMC 75005 Paris France"},{"name":"Department of Fundamental Neurosciences The University of Lausanne Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4730-2474","authenticated-orcid":false,"given":"Frank J.","family":"Meye","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience Brain Center Rudolf Magnus UMC Utrecht Universiteitsweg 100 3584 CG Utrecht The 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