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Keywords:

  • 5-HT1 receptor;
  • drug overuse;
  • protein extravasation;
  • triptan;
  • vasoconstriction

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Triptans are commonly used anti-migraine drugs and show agonist action mainly at serotonin 5-HT1B/1D/1F receptors. It is not known whether frequent or long-term treatment with these drugs would alter 5-HT receptor function. We investigated the effects of protracted (14–18 days) sumatriptan and zolmitriptan treatment  in rats on 5-HT1 receptor mRNA expression and function in tissues related to migraine pathophysiology. RT-PCR analysis revealed that 5-HT1B/1D/1F receptor mRNA was reduced in the trigeminal ganglion after treatment with either triptan (reduction by: sumatriptan 39% and zolmitriptan 61% for 5-HT1B; 60%vs 41% for 5-HT1D; 32%vs 68% for 5-HT1F). Sumatriptan attenuated 5-HT1D receptor mRNA by 49% in the basilar artery, whereas zolmitriptan reduced 5-HT1B mRNA in this tissue by 70%. No change in 5-HT1 receptor mRNA expression was observed in coronary artery and dura mater. Chronic triptan treatment had no effect in two functional assays [sumatriptan mediated inhibition (50 mg/kg, i.p.) of electrically induced plasma protein extravasation in dura mater and 5-nonyloxytryptamine-stimulated [35S]guanosine-5′-O-(3-thio)triphosphate binding in substantia nigra]. Furthermore, vasoconstriction to 5-HT in isolated basilar artery was not affected by chronic triptan treatment, while it was slightly reduced in coronary artery. We conclude that, although our treatment protocol altered mRNA receptor expression in several tissues relevant to migraine pathophysiology, it did not attenuate 5-HT1 receptor-dependent  functions  in  rats.