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 KCl, 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 the hyperperfusion amplitude during CSD by approximately 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 micrograms/kg i.v. (n=5) had no effect on CSD hyperperfusion, while 800 micrograms/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.
Gold
L
L
Department of Neurology, Charité Hospital, Humboldt University, Berlin, Germany.
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Arnold
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Dreier
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Einhäupl
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Reuter
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Dirnagl
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D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D006940:Hyperemia / Q000503:physiopathology*; D008297:Male; D008881:Migraine Disorders / Q000503:physiopathology; D010080:Oxazoles / Q000494:pharmacology; D023303:Oxazolidinones; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000502:physiology; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014363:Tryptamines
D010080:Oxazoles; D023303:Oxazolidinones; D044302:Receptor, Serotonin, 5-HT1B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; D016713:Ritanserin; C089750:zolmitriptan; D012701:Serotonin