{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T23:55:01Z","timestamp":1770681301801,"version":"3.49.0"},"reference-count":63,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,9,5]],"date-time":"2019-09-05T00:00:00Z","timestamp":1567641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007132","name":"Otsuka Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007132","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropsychopharm Rep"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Long\u2010term antipsychotic treatment in patients with schizophrenia can induce supersensitivity psychosis and tardive dyskinesia which is thought to be caused by dopamine D<jats:sub>2<\/jats:sub> receptor sensitization. We evaluated the effects of brexpiprazole on D<jats:sub>2<\/jats:sub> receptor sensitivity after subchronic treatment in rats. We also evaluated whether brexpiprazole could suppress enhanced response to D<jats:sub>2<\/jats:sub> receptors in rats subchronically dosed with another atypical antipsychotic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The maximum D<jats:sub>2<\/jats:sub> receptor density (<jats:italic>B<\/jats:italic><jats:sub>max<\/jats:sub>) and apomorphine (a D<jats:sub>2<\/jats:sub> receptor agonist)\u2010induced stereotypy were measured in rats orally dosed with vehicle, haloperidol (1\u00a0mg\/kg), or brexpiprazole (4 or 30\u00a0mg\/kg for <jats:italic>B<\/jats:italic><jats:sub>max<\/jats:sub>, 6 or 30\u00a0mg\/kg for stereotypy) for 21\u00a0days. Then, effects of oral administrations of brexpiprazole (3\u00a0mg\/kg), aripiprazole (10\u00a0mg\/kg), and olanzapine (3\u00a0mg\/kg) against increases in apomorphine\u2010induced hyperlocomotion and (\u00b1)\u20102,5\u2010dimethoxy\u20104\u2010iodoamphetamine hydrochloride (DOI: a 5\u2010HT<jats:sub>2A<\/jats:sub> receptor agonist)\u2010induced head twitches were evaluated in rats subcutaneously treated with risperidone (1.5\u00a0mg\/kg\/d) via minipumps for 21\u00a0days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Haloperidol and brexpiprazole (30\u00a0mg\/kg: approximately tenfold ED<jats:sub>50<\/jats:sub> of anti\u2010apomorphine\u2010induced stereotypy) but not brexpiprazole (4 or 6\u00a0mg\/kg) significantly increased the <jats:italic>B<\/jats:italic><jats:sub>max<\/jats:sub> and apomorphine\u2010induced stereotypy. Brexpiprazole (3\u00a0mg\/kg) and olanzapine (3\u00a0mg\/kg) significantly suppressed both increases in apomorphine\u2010induced hyperlocomotion and also DOI\u2010induced head twitches in rats subchronically treated with risperidone, but aripiprazole (10\u00a0mg\/kg) significantly suppressed only apomorphine\u2010induced hyperlocomotion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Brexpiprazole has a low risk of D<jats:sub>2<\/jats:sub> receptor sensitization after a repeated administration and suppresses the rebound phenomena related to D<jats:sub>2<\/jats:sub> and 5\u2010HT<jats:sub>2A<\/jats:sub> receptors after a repeated administration of risperidone.<\/jats:p><\/jats:sec>","DOI":"10.1002\/npr2.12076","type":"journal-article","created":{"date-parts":[[2019,9,5]],"date-time":"2019-09-05T18:08:48Z","timestamp":1567706928000},"page":"279-288","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Brexpiprazole has a low risk of dopamine D<sub>2<\/sub> receptor sensitization and inhibits rebound phenomena related to D<sub>2<\/sub> and serotonin 5\u2010HT<sub>2A<\/sub> receptors in rats"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9625-6240","authenticated-orcid":false,"given":"Naoki","family":"Amada","sequence":"first","affiliation":[{"name":"Department of CNS Research Otsuka Pharmaceutical Co., Ltd. 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