Role of 5-HT2 receptors in the tryptamine-induced 5-HT syndrome in rats.

摘要

We distinguished the functions of the different 5-hydroxytryptamine-2 (5-HT ) receptor (5-HT R) subtypes in the tryptamine-induced 5-HT syndrome in rats using (1) the 5-HT R antagonist R93274 ( -[(3- -fluorophenyl-1-propyl)-4-methyl-4-piperidinyl]-4-amino-5-iodo-2-methoxybe nzamide), the 5-HT R antagonist R99647 (2-(dimethylaminomethyl)2,3,3,8-tetrahydrodibenzo[ ]isoxazolo[2,3- ]azepine), the 5-HT R antagonist SB-242084 (6-chloro-5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-in doline), and several 5-HT R antagonists (ketanserin, risperidone, pipamperone and mianserin); and (2) chronic 5-HT R activation by 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM). In contrast to SB-242084, the selective 5-HT R antagonist R93274 as well as the non-selective 5-HT R antagonists (R99647, ketanserin, risperidone, pipamperone and mianserin) significantly inhibited tryptamine-induced forepaw treading and tremors, and reversed peripherally mediated cyanosis into hyperaemia; only the 5-HT R antagonists R99647 and mianserin inhibited the tryptamine-induced hunched back. Intermittent DOM administration (intravenously every 48 h for 12 days) did not change the centrally mediated tryptamine-induced forepaw treading, tremors and hunched back at 1, 4 or 7 days after the last DOM pretreatment. The DOM-induced head twitch response, measured immediately after every DOM injection, was not affected. In contrast, peripherally mediated cyanosis was reversed into hyperaemia in 75, 11 and 20% of all pretreated rats at 1, 4 and 7 days, respectively, after the last DOM administration. Taken together, these finding suggest that central 5-HT Rs mediate tryptamine-induced forepaw treading and tremors, that peripheral 5-HT Rs mediate tryptamine-induced cyanosis, and that 5-HT Rs mediate tryptamine-induced hunched back. Peripheral 5-HT Rs are more sensitive to desensitization after intermittent treatment with an agonist than central 5-HT Rs.(2) (2) (2A) (2A/C) (2B/C) (2) (2) (2A) (2A) (2A/C) (2A) (2A) (2C) (2A) (2A)