{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T17:57:24Z","timestamp":1760551044712,"version":"3.41.2"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T00:00:00Z","timestamp":1580256000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA 034192","R21 DA 034192"],"award-info":[{"award-number":["DA 034192","R21 DA 034192"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000874","name":"Brain and Behavior Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000874","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016506","name":"Alcohol and Drug Abuse Institute, University of Washington","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016506","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A major problem in the treatment of cocaine addiction is high rates of relapse. Relapse is often provoked by acute reexposure to cocaine\u2010associated cues or to cocaine itself. The lateral habenula (LHb), an epithalamic nucleus, regulates midbrain dopaminergic systems that are known to be involved in cocaine taking and seeking behaviors. However, the role of this nucleus in cocaine self\u2010administration and reinstatement of cocaine seeking has not been entirely parsed out. We used an operant self\u2010administration and reinstatement procedure to explore the effect of Designer Receptors Exclusively Activated by Designer Drug (DREADD)\u2010induced transient inhibition of LHb neurons on cocaine taking and seeking. Firstly, rats were injected with adeno\u2010associated viral vectors expressing hM<jats:sub>4<\/jats:sub>D<jats:sub>i<\/jats:sub> (a G<jats:sub>i\/o<\/jats:sub>\u2010coupled DREADD) into the LHb, trained to self\u2010administer cocaine (0.75 mg\/kg\/infusion), and the effect of clozapine\u2010N\u2010oxide (an inert ligand that activates DREADDs) was assessed on cocaine self\u2010administration. Secondly, rats were injected with hM<jats:sub>4<\/jats:sub>D<jats:sub>i<\/jats:sub> into the LHb, trained to self\u2010administer cocaine; the operant response was extinguished, and cue\u2010 and cocaine priming\u2010induced reinstatement was assessed. Thirdly, we tested the generality of the effect of inhibiting LHb neurons by assessing the effect of this manipulation on food\u2010taking and seeking. hM<jats:sub>4<\/jats:sub>D<jats:sub>i<\/jats:sub>\u2010induced inhibition of LHb neurons increased cocaine but not food self\u2010administration. In contrast, this manipulation decreased reinstatement of cocaine, but not food\u2010seeking. Taken together, our data suggest that hM<jats:sub>4<\/jats:sub>D<jats:sub>i<\/jats:sub>\u2010 induced LHb inhibition specifically mediates taking and seeking behaviors reinforced by cocaine but not by natural reinforcers. Further, our data indicate a dissociation in the role of LHb neurons on cocaine self\u2010administration versus reinstatement of cocaine seeking.<\/jats:p>","DOI":"10.1111\/adb.12865","type":"journal-article","created":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T08:46:53Z","timestamp":1580287613000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Effect of chemogenetic inhibition of lateral habenula neuronal activity on cocaine\u2010 and food\u2010seeking behaviors in the rat"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0998-1629","authenticated-orcid":false,"given":"Sunila G.","family":"Nair","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Harborview Medical Sciences University of Washington  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis 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