5-HT(1A) and 5-HT(1B/1D) receptors are involved in the modulation of the trigeminovascular system of the cat: a microiontophoretic study

Electrical stimulation of the superior sagittal sinus in the cat activated neurones in the trigeminal nucleus caudalis. The mean latency of these responses (10.1 ms) was consistent with activation of Adelta-fibres. Microiontophoretic ejection of either the selective serotonin(1A) (5-HT(1A)) agonist (+)8-OH-DPAT or the 5-HT(1B/1D) agonist alniditan resulted in the reversible suppression of the response to superior sagittal sinus stimulation of 29/46 and 18/20 trigeminal neurones, respectively. The response to sagittal sinus stimulation was suppressed by 39+/-5% (n=46) by (+)8-OH-DPAT and 65+/-5% (n=20) by alniditan. Microiontophoretic ejection of the selective 5-HT(1A) receptor antagonist WAY-100635 significantly antagonised the effect of (+)8-OH-DPAT (effect reduced by 30%, P<0.05). The ejection of GR-127935, a selective 5-HT(1B/1D), antagonist, significantly antagonised the effect of alniditan (effect reduced by 52%, P<0.02). In eight neurones the response to convergent facial receptive field stimulation was also tested in the presence of alniditan. Only 4/8 receptive field responses were suppressed by alniditan (compared to 8/8 sagittal sinus responses) and alniditan had significantly less quantitative effect on the response to receptive field stimulation than on the response to sagittal sinus stimulation in the same neurones (mean reduction 36+/-14% and 66+/-8%, respectively, P<0.05). These results suggest that pharmacological modulation of the trigeminovascular system can occur at the first central synapse and that, in addition to 5-HT(1B/1D) receptors, 5-HT(1A) receptors may be involved in the modulation of sensory neurotransmission in the trigeminovascular system.