5-Hydroxytryptamine agonistic action of methysergide and the absence of supersensitivity to 5-HT agonists in spinal flexor reflexes in rats.
The intravenous administration of L-5-hydroxytryptophan (5-HTP), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), p-chloroamphetamine (PCA), LSD and methysergide to acute spinal rats, transected at C1, stimulated the flexor reflexes induced by electrical stimulation applied to the skin of the toe. The enhancement produced by 5-HTP, 5-MeODMT and PCA, was not antagonized by the prior administration of a dose of LSD or methysergide, although the enhancement produced by 5-MeODMT, LSD and methysergide, but not that produced by 5-HTP and PCA, was antagonized by cyproheptadine. In rats treated with 5,6-dihydroxytryptamine (intracisternal administration, 2 weeks previously) supersensitivity was observed to the effects of 5-HTP, a precursor of 5-HT, while subsensitivity was observed for the effects of PCA, a releaser of 5-HT. However, no supersensitivity was observed for the effects of 5-MeODMT, LSD and methysergide. These results suggest that methysergide may have an agonistic action on the 5-HT receptors in spinal cord and that supersensitivity to 5-HTP in rats treated with 5,6-dihydroxytryptamine was due to the lack of uptake of 5-HT into terminals of descending 5-HT fibres or to the change in 5-HT receptors which were not sensitive to 5-MeODMT, LSD, methysergide or cyproheptadine.
Ono
H
H
Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Miyamoto
M
M
Kobayashi
M
M
Fukuda
H
H
D015115:5,6-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D003533:Cyproheptadine / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D013268:Stimulation, Chemical
D003533:Cyproheptadine; D012701:Serotonin; D008238:Lysergic Acid Diethylamide; D015115:5,6-Dihydroxytryptamine; D008784:Methysergide