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  • Title: Comparison of the effects of central and peripheral dopamine receptor activation on evoked firing in the trigeminocervical complex.
    Author: Charbit AR, Akerman S, Goadsby PJ.
    Journal: J Pharmacol Exp Ther; 2009 Nov; 331(2):752-63. PubMed ID: 19657051.
    Abstract:
    Dopaminergic mechanisms have been suggested to play a role in migraine. Here, electrophysiological techniques were used to study the effects of intravenously administered centrally or peripherally active dopamine receptor agonists and antagonists on evoked firing in the trigeminocervical complex (TCC). After establishing baseline firing evoked by electrical stimulation of the dural middle meningeal artery (MMA) and mechanical noxious and innocuous stimulation of the ophthalmic dermatome, D(1)- or D(2)-like receptor agonists or antagonists were administered intravenously and the effect on firing was determined. In addition, with use of intravital microscopy, we monitored changes in dural vessel diameter in response to varying doses of D(1)- or D(2)-like receptor agonists to determine whether their effects were related to blood vessel caliber. The central D(2)-like receptor agonist quinpirole hydrochloride inhibited firing in the TCC evoked by stimulation of the MMA. Conversely, the central D(2)-like receptor antagonists, eticlopride hydrochloride and remoxipride hydrochloride, facilitated MMA-evoked firing and also firing evoked by noxious and innocuous stimulation of the ophthalmic dermatome. Both the peripheral D(1)-like receptor agonist fenoldopam and the central D(1)-like receptor agonists cis-(+/-)-1-(aminomethyl)-3,4-dihydro-3-phenyl-1H-2-benzopyran-5,6-diol hydrochloride (A68930 hydrochloride) and dihydrexidine facilitated innocuous brush-evoked firing, with A68930 hydrochloride having the greatest effect. The data suggest that dopamine binding to peripheral D(1)-like receptors may play a role in peripheral sensitization, and that the inhibitory or excitatory effects seen with administration of dopamine receptor agonists are independent of blood vessel changes. In addition, these studies maintain that central D(2)-like receptors inhibit trigeminocervical neurons, and may provide insight into the conflicting literature on the role of dopamine and its receptors in migraine.
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