Cortical spreading depression-associated hyperemia in rats:: involvement of serotonin

We investigated whether the vasoactive neurotransmitter serotonin (5-HT) is involved in cortical spreading depression (CSD)-associated hyperemia in the rat. We focused on the 5-HT2 receptor, which is engaged in 5-HT induced small arteriolar relaxation in cats, as well as on the 5-HT1D/1B receptor, the binding site of the potent antimigraine drug sumatriptan. In male barbiturate anaesthetized Wistar rats (n = 25) CSDs were elicited by brain topical application of 1 M KCI, and the DC-potential and regional cerebral blood flow (rCBF, by Laser Doppler flowmetry) were measured over the same hemisphere through dura and thinned bone, respectively. Intravenous application of 8 mg/kg of the 5-HT2A/2C receptor antagonist ritanserin (group I; n = 8) significantly reduced thr hyperperfusion amplitude during CSD by similar to 44% (p < 0.05, from 342 +/- 124 to 194 +/- 97%, baseline before CSD = 100%), and prolonged its duration by approx. 30%. Vehicle alone (group II; n = 4) did not affect CSD hyperperfusion. The highly selective 5-HT1D/1B receptor agonist 311C90 was given in two doses: 100 mu g/kg i.v. (n = 5) had no effect on CSD hyperperfusion, while 800 mu g/kg (n = 5) increased hyperperfusion significantly (p < 0.05, from 224 +/- 86 to 310 +/- 148%). We conclude that serotonin is, probably via 5-HT2 receptors, involved in the modulation of the regional cerebral blood flow increase during CSD. Novel highly selective receptor antagonists may help to discriminate the differential contribution of various 5-HT receptor subspecies. (C) 1998 Elsevier Science B.V.