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This study investigates how cariprazine modulates affective and social behaviors through D3 neurons in the olfactory tubercle (OT). Local infusion of cariprazine specifically into the OT, but not the nucleus accumbens (NAc) or hippocampus, induced anxiety-like behaviors, impaired struggling behaviors in depression-related tests, and increased huddling behavior, a measure of thermoregulation and social interaction. These behavioral changes were associated with decreased D3 neuronal activity in the OT, as evidenced by whole-cell patch-clamp recordings. Optogenetic activation of OT D3 neurons normalized cariprazine-induced anxiety-like behaviors and blunted the increase in struggling and huddling behavior. Additionally, cariprazine administration elevated body temperature, likely due to enhanced huddling behavior. These findings underscore the critical role of OT D3 neurons in mediating cariprazine\u2019s effects on affective and social behaviors, providing new insights into the neural mechanisms underlying its therapeutic actions and the involvement of ventral striatal D3 neurons in neuropsychiatric disorders.<\/jats:p>","DOI":"10.1093\/cz\/zoaf034","type":"journal-article","created":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T07:45:05Z","timestamp":1749282305000},"page":"198-210","source":"Crossref","is-referenced-by-count":0,"title":["Cariprazine modulates affective and social behaviors through ventral striatal islands of Calleja neurons"],"prefix":"10.1093","volume":"72","author":[{"given":"Zhangwei","family":"Song","sequence":"first","affiliation":[{"name":"Department of Ultrasound, The Second Affiliated Hospital and Yuying Children\u2019s Hospital, Wenzhou Medical University , Wenzhou 325027 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 ,","place":["China"]},{"name":"School of Life Sciences, Hebei University , Baoding 071002 ,","place":["China"]},{"name":"Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Chinese Academy of Sciences , Beijing 100101 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiping","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 ,","place":["China"]},{"name":"Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Chinese Academy of Sciences , Beijing 100101 ,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing 100101 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbiao","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, The First Affiliated Hospital of Gannan Medical University , Ganzhou 341000 ,","place":["China"]},{"name":"Ganzhou Intelligent Rehabilitation Technology Innovation Center , Ganzhou 341000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanqing","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 ,","place":["China"]},{"name":"School of Life Sciences, Hebei University , Baoding 071002 ,","place":["China"]},{"name":"Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Chinese Academy of Sciences , Beijing 100101 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiyi","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Peking University People\u2019s Hospital , Beijing 100044 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6324-4115","authenticated-orcid":false,"given":"Yun-Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 ,","place":["China"]},{"name":"Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Chinese Academy of Sciences , Beijing 100101 ,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing 100101 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