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Despite abundant research in multifaceted therapeutic strategies, a high rate of relapse still characterises this condition. Dopamine D<jats:sub>3<\/jats:sub> receptor antagonists combined with cue\u2010exposure therapies have been proposed to ameliorate the abused drugs\u2010induced cognitive deficits, which consequently would aid to prevent the maladaptive behaviours responsible for drug use.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We used the morphine withdrawal\u2010induced conditioned place aversion (CPA) paradigm to assess, in male rats, the efficacy of D<jats:sub>3<\/jats:sub> receptor blockade to improve the extinction of drug\u2010seeking behaviours associated with the aversive contextual stimuli of its withdrawal. Then, using immunohistochemical methods, we evaluated the participation of neuroimmune mechanisms in the striatum and infralimbic cortex in D<jats:sub>3<\/jats:sub> receptor modulation of CPA extinction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Whereas the selective D<jats:sub>3<\/jats:sub> antagonist PG01037 accelerated the extinction of the morphine withdrawal\u2010induced CPA, our findings indicate that decreased motivation might be involved in this action. Increased D<jats:sub>3<\/jats:sub> receptor expression in glial cells and the modulation of microglia activation state in specific dopaminoceptive areas could intervene in the behavioural outcomes of D<jats:sub>3<\/jats:sub> receptor blockade.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Our findings reveal a facilitatory role of D<jats:sub>3<\/jats:sub> antagonists in the inhibition of morphine\u2010seeking behaviours triggered by contextual stimuli associated with its withdrawal. Nonetheless, their potential ability to reduce motivation might influence their therapeutic use. Future investigations elucidating the precise function of D<jats:sub>3<\/jats:sub> receptors will facilitate the identification of this receptor as a valuable therapeutic target for mitigating the recurrence of opioid withdrawal\u2010induced drug\u2010seeking behaviour.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.70081","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T01:21:02Z","timestamp":1747876862000},"page":"4168-4185","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dopamine D<sub>3<\/sub> receptor blockade accelerates the extinction of opioid withdrawal\u2010induced drug\u2010seeking behaviours and alters microglia in dopaminoceptive nuclei"],"prefix":"10.1111","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6141-2303","authenticated-orcid":false,"given":"Aurelio","family":"Franco\u2010Garc\u00eda","sequence":"first","affiliation":[{"name":"Group of Cellular and Molecular Pharmacology, Department of Pharmacology, CEIR Campus Mare Nostrum University of Murcia  Murcia Spain"},{"name":"Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB) \u2013 Pascual Parrilla  Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4626-2674","authenticated-orcid":false,"given":"Victoria","family":"G\u00f3mez\u2010Murcia","sequence":"additional","affiliation":[{"name":"Group of Cellular and Molecular Pharmacology, Department of Pharmacology, CEIR Campus Mare Nostrum University of Murcia  Murcia Spain"},{"name":"Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB) \u2013 Pascual Parrilla  Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0984-2218","authenticated-orcid":false,"given":"M. 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