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

• Published in: Brain research Vol. 783; no. 2; pp. 188 - 193
• Main Authors: Gold, Lorenz, Back, Tobias, Arnold, Guy, Dreier, Jens, Einhäupl, Karl M, Reuter, Uwe, Dirnagl, Ulrich
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 09.02.1998; Amsterdam Elsevier; New York, NY
• Subjects: 5-Hydroxytryptamine; Animals; Biological and medical sciences; Brain; Central nervous system; Cerebral blood flow; Cerebrovascular Circulation - drug effects; Cerebrovascular Circulation - physiology; Cortical Spreading Depression - drug effects; Cortical Spreading Depression - physiology; Electrophysiology; Fundamental and applied biological sciences. Psychology; Hyperemia - physiopathology; Male; Migraine; Migraine Disorders - physiopathology; Oxazoles - pharmacology; Oxazolidinones; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT1B; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin - physiology; Ritanserin; Ritanserin - pharmacology; Serotonin - physiology; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology; Tryptamines; Vertebrates: nervous system and sense organs; 5-Hydroxytryptamine; Brain; Cerebral blood flow; Migraine; Ritanserin; Regional blood flow; Cerebral cortex; Rat; Serotonin; Rodentia; Central nervous system; Electrophysiology; Electroencephalography; Reactive hyperemia; Vertebrata; Mammalia; Neurotransmitter; Hemodynamics; Spreading depression; Brain (vertebrata)
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(97)01341-3

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-HT 2 receptor, which is engaged in 5-HT induced small arteriolar relaxation in cats, as well as on the 5-HT 1D/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-HT 2A/2C receptor antagonist ritanserin (group I; n=8) significantly reduced the hyperperfusion amplitude during CSD by ∼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-HT 1D/1B receptor agonist 311C90 was given in two doses: 100 μg/kg i.v. ( n=5) had no effect on CSD hyperperfusion, while 800 μg/kg ( n=5) increased hyperperfusion significantly ( p<0.05, from 224±86 to 310±148%). We conclude that serotonin is, probably via 5-HT 2 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.