{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:03:57Z","timestamp":1768507437599,"version":"3.49.0"},"posted":{"date-parts":[[2023,10,6]]},"group-title":"Neuroscience","reference-count":41,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,10,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Addiction is marked by aberrant decision-making and an inability to suppress inappropriate and often dangerous behaviors. We previously demonstrated that inactivation of the rostromedial tegmental nucleus (RMTg) in rats causes persistent food seeking despite impending aversive footshock, an effect strikingly similar to the punishment resistance observed in people with a history of protracted drug use [1]. Here, we extend these studies to demonstrate chemogenetic silencing of RMTg axonal projections to the ventral tegmental area (VTA) (RMTg\u25caVTA pathway) causes rats to endure significantly more footshock to receive cocaine infusions. To further test whether activation of this circuit is sufficient to suppress reward seeking in the absence of an overtly aversive stimulus, we used temporally specific optogenetic stimulation of the RMTg\u25caVTA pathway as a \u201cpunisher\u201d in place of footshock following lever pressing for either food or cocaine reward. While optical stimulation of the RMTg\u25caVTA pathway robustly suppressed lever pressing for food, we found that stimulation of this circuit had only modest effects on suppressing responding for cocaine infusions. Even though optical RMTg\u25caVTA stimulation was not particularly effective at reducing\n                  <jats:italic>ongoing<\/jats:italic>\n                  cocaine use, this experience nevertheless had long-lasting consequences, as reinstatement of drug seeking in response to cocaine-associated cues was profoundly suppressed when tested nearly two weeks later. These results suggest the RMTg may serve as a useful target for producing enduring reductions in drug craving, particularly during periods of abstinence from drug use.\n                <\/jats:p>","DOI":"10.1101\/2023.10.04.560908","type":"posted-content","created":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T08:13:53Z","timestamp":1696839233000},"source":"Crossref","is-referenced-by-count":0,"title":["Pumping the brakes: rostromedial tegmental inhibition of compulsive cocaine seeking"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7279-8790","authenticated-orcid":false,"given":"Peter J.","family":"Vento","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob R.","family":"Watson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominika","family":"Pullmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha L.","family":"Black","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jensen S.","family":"Tomberlin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas C.","family":"Jhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023101013500962000_2023.10.04.560908v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3119"},{"key":"2023101013500962000_2023.10.04.560908v1.2","doi-asserted-by":"publisher","DOI":"10.1007\/s11920-011-0224-0"},{"key":"2023101013500962000_2023.10.04.560908v1.3","doi-asserted-by":"publisher","DOI":"10.1007\/PL00005483"},{"key":"2023101013500962000_2023.10.04.560908v1.4","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-007-1051-1"},{"issue":"4","key":"2023101013500962000_2023.10.04.560908v1.5","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s00702-018-1957-2","article-title":"Dopamine and addiction: what have we learned from 40 years of research","volume":"126","year":"2019","journal-title":"J Neural Transm (Vienna"},{"key":"2023101013500962000_2023.10.04.560908v1.6","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2008.0089"},{"key":"2023101013500962000_2023.10.04.560908v1.7","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-015-0997-8"},{"key":"2023101013500962000_2023.10.04.560908v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2016.10.018"},{"issue":"5","key":"2023101013500962000_2023.10.04.560908v1.9","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.neuron.2019.08.040","article-title":"Three Rostromedial Tegmental Afferents Drive Triply Dissociable Aspects of Punishment Learning and Aversive Valence Encoding","volume":"104","year":"2019","journal-title":"Neuron"},{"key":"2023101013500962000_2023.10.04.560908v1.10","doi-asserted-by":"crossref","unstructured":"Wilczkowski, M. , et al., Recruitment of inhibitory neuronal pathways regulating dopaminergic activity for the control of cocaine seeking. 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