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We found that adolescent THC administration potentiated reward, and paradoxically impaired the development of morphine reward. Following a forced abstinence period, we then mapped the whole-brain response to a moderate dose of morphine, and found that adolescent THC administration led to increased morphine-induced activity in the basal ganglia and increased functional connectivity between frontal cortical regions and the ventral tegmental area. Last, we show using rabies virus-based circuit mapping that adolescent THC exposure triggers a long-lasting elevation in connectivity from the frontal cortex regions onto ventral tegmental dopamine cells. Our study adds to the rich literature on the interaction between drugs of abuse, including THC and opioids, and provides potential circuit substates by which adolescent THC exposure influences responses to morphine later in life.<\/jats:p>","DOI":"10.1101\/2024.04.23.590773","type":"posted-content","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T01:10:15Z","timestamp":1714093815000},"source":"Crossref","is-referenced-by-count":0,"title":["Neural circuit basis of adolescent THC-induced potentiation of opioid responses later in life"],"prefix":"10.64898","author":[{"given":"Elizabeth","family":"Hubbard","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivienne Mae","family":"Galinato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pieter","family":"Derdeyn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrina","family":"Bartas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen V.","family":"Mahler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4934-1338","authenticated-orcid":false,"given":"Kevin T.","family":"Beier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024050805592525000_2024.04.23.590773v2.1","unstructured":"National Center for Drug Abuse Statistics. 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