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It has been suggested that the lateral hypothalamus (LH) or lateral habenula (LHb) is involved in drug\u2010seeking behaviours. To explore the role of the LH and the LHb in cocaine\u2010induced psychomotor responses, we tested whether modulation of the LH or the LH\u2010LHb circuit affects cocaine\u2010induced locomotion. Cocaine\u2010induced locomotor activity and dopamine release were suppressed by the activation of the LH with 2\u2010[2,6\u2010difluoro\u20104\u2010[[2\u2010[(phenylsulfonyl)amino]ethyl]thio]phenoxy]acetamide (PEPA), an AMPA receptor agonist. When the LH was inhibited by microinjection of a GABA receptor agonists mixture prior to cocaine injection, the cocaine's effects were enhanced. Furthermore, optogenetic activation of the LH\u2010LHb circuit attenuated the cocaine\u2010induced locomotion, while optogenetic inhibition of the LH\u2010LHb circuit increased it. <jats:italic>In vivo<\/jats:italic> extracellular recording found that the LH sent a glutamatergic projection to the LHb. These findings suggest that the LH glutamatergic projection to the LHb plays an active role in the modulation of cocaine\u2010induced psychomotor responses.<\/jats:p>","DOI":"10.1111\/adb.13354","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T20:52:31Z","timestamp":1699044751000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A hypothalamus\u2010habenula circuit regulates psychomotor responses induced by cocaine"],"prefix":"10.1111","volume":"28","author":[{"given":"Dan Bi","family":"Ahn","sequence":"first","affiliation":[{"name":"Department of Physiology Yonsei University College of Medicine  Seoul South Korea"},{"name":"Department of Physiology, College of Korean Medicine Daegu Haany University  Daegu South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han Byeol","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of 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