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Dopaminergic agonist apomorphine, D2 receptor antagonists metoclopramide and haloperidol and 5\u2010HT3 receptor antagonist ondansetron alone and together were tested in nitroglycerin\u2010induced migraine model, in vivo. Likewise, the combinations of drugs were also tested on basal calcitonin gene\u2010related peptide (CGRP) release in vitro hemiskull preparations. Mechanical allodynia was tested by von Frey filaments. CGRP concentrations in trigeminovascular structures and in vitro superfusates and c\u2010Fos levels in the brainstem were determined by enzyme\u2010linked immunosorbent assay. Meningeal mast cells were evaluated with toluidine blue staining. Apomorphine further enhanced nitroglycerin\u2010induced mechanical allodynia, brainstem c\u2010fos expression, trigeminal ganglion and brainstem CGRP concentrations and meningeal mast cell degranulation, in vivo. Haloperidol completely antagonised all apomorphine\u2010induced effects and also alleviated changes induced by nitroglycerin without apomorphine. Metoclopramide and ondansetron partially attenuated apomorphine\u2010 or nitroglycerin\u2010induced effects. A combination of haloperidol and ondansetron decreased basal CGRP release, in vitro, whereas the other administrations were ineffective. Apomorphine\u2010mediated dopaminergic activation exacerbated nitroglycerin\u2010stimulated nociceptive reactions by further enhancing c\u2010fos expression, CGRP release and mast cell degranulation in strategical structures associated with migraine pain. Metoclopramide partially attenuated the effects of apomorphine, most likely because it is also a 5\u2010HT3 receptor antagonist. Haloperidol with pure D2 receptor antagonism feature appears to be more effective than metoclopramide in reducing migraine\u2010related parameters in dopaminergic activation\u2010 and\/or NTG\u2010induced migraine\u2010like conditions.<\/jats:p>","DOI":"10.1111\/ejn.16106","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T09:34:45Z","timestamp":1691141685000},"page":"1177-1193","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["D2 dopamine receptor\u2010mediated mechanisms of dopaminergic system modulation in in vivo and in vitro experimental models of migraine"],"prefix":"10.1111","volume":"59","author":[{"given":"Yasemin","family":"Baranoglu Kilinc","sequence":"first","affiliation":[{"name":"Department of Pediatrics Bolu Izzet Baysal State Hospital  Bolu Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim 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