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To date, however, the neural circuits involved in the allocation of behavior have not been systematically evaluated. Herein, a chemogenetics approach (i.e., designer receptors exclusively activated by designer drugs (DREADDs)) was utilized in combination with a concurrent choice self-administration experimental paradigm to evaluate the role of the mesolimbic neurocircuit in the allocation of behavior. Pharmacological activation of hM3D(G\n                    <jats:sub>q<\/jats:sub>\n                    ) DREADDs in neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens (AcbSh) induced a sex-dependent shift in the allocation of behavior in rodents transduced with DREADDs. Specifically, male DREADDs animals exhibited a robust increase in responding for a natural (i.e., sucrose) reward following pharmacological activation of the VTA-AcbSh circuit; female DREADDs rodents, in sharp contrast, displayed a prominent decrease in drug-reinforced (i.e., cocaine) responding. The sequential activation of hM3D(G\n                    <jats:sub>q<\/jats:sub>\n                    ) and KORD DREADDs within the same neuronal population validated the role of the VTA-AcbSh circuit in reinforced responding for concurrently available natural and drug rewards. Collectively, the VTA-AcbSh circuit is fundamentally involved in behavioral allocation affording a key target for the development of novel pharmacotherapies.\n                  <\/jats:p>","DOI":"10.1515\/nipt-2025-0002","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T04:00:13Z","timestamp":1750996813000},"page":"237-252","source":"Crossref","is-referenced-by-count":0,"title":["Sex-dependent modulation of behavioral allocation via ventral tegmental area-nucleus accumbens shell circuitry"],"prefix":"10.1515","volume":"4","author":[{"given":"Kristen A.","family":"McLaurin","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences , College of Pharmacy, University of Kentucky , Lexington , KY , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica M.","family":"Illenberger","sequence":"additional","affiliation":[{"name":"Cognitive and Neural Science Program, Department of Psychology , Barnwell College, University of South Carolina , Columbia , SC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hailong","family":"Li","sequence":"additional","affiliation":[{"name":"Cognitive and Neural Science Program, Department of Psychology , Barnwell College, University of South Carolina , Columbia , SC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosemarie M.","family":"Booze","sequence":"additional","affiliation":[{"name":"Cognitive and Neural Science Program, Department of Psychology , Barnwell College, University of South Carolina , Columbia , SC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles F.","family":"Mactutus","sequence":"additional","affiliation":[{"name":"Cognitive and Neural Science Program, Department of Psychology , Barnwell College, University of South Carolina , Columbia , SC , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"2025072913052724668_j_nipt-2025-0002_ref_001","unstructured":"Substance Abuse and Mental Health Services Administration. 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