PT - JOURNAL ARTICLE AU - Akerman, S. AU - Goadsby, P. J. TI - The Role of Dopamine in a Model of Trigeminovascular Nociception AID - 10.1124/jpet.105.083139 DP - 2005 Jul 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 162--169 VI - 314 IP - 1 4099 - http://jpet.aspetjournals.org/content/314/1/162.short 4100 - http://jpet.aspetjournals.org/content/314/1/162.full SO - J Pharmacol Exp Ther2005 Jul 01; 314 AB - Migraine is a common, disabling problem with three phases: premonitory, main headache attack, and postdrome. The headache phase is thought to involve activation of trigeminal neurons, whereas the premonitory and postdrome phases may involve dopaminergic mechanisms. In animal studies, dopamine has been found to cause vasodilation of cranial arteries at very low doses. Using intravital microscopy, we examined the effect of dopamine receptor agonists on dural blood vessel caliber and the effect of dopamine and specific dopamine receptor antagonists on trigeminovascular neurogenic dural vasodilation. Dopamine hydrochloride caused a significant vasoconstriction (P < 0.05) and increase in arterial blood pressure (P < 0.05) that was reversed by a α2-adrenoceptor antagonist, yohimbine, rather than specific dopamine receptor antagonists. The D1 receptor agonist caused a vasoconstriction (P < 0.05) and a blood pressure increase (P < 0.05), which was reversed by yohimbine and therefore α2-adrenoceptor-mediated. None of the specific dopamine receptor antagonists were able to attenuate neurogenic dural vasodilation. Dopamine hydrochloride infusion (P < 0.05) and a D1 receptor agonist were able to attenuate the vasodilation (P < 0.05), with maximal dilation returning after cessation of the dopamine agonist infusion. This response may be due to the vasoconstrictor effects of the α2-adrenoceptor and an action at the D1 receptor. In the intravital model of trigeminal activation, it seems that dopamine receptors do not play a major role and may not present an acute treatment option. Our data do not exclude a role for dopamine receptor modulators in short- or long-term prevention. The American Society for Pharmacology and Experimental Therapeutics