期刊
BEHAVIOURAL PHARMACOLOGY
卷 13, 期 4, 页码 313-318出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00008877-200207000-00008
关键词
5-HT syndrome; 5-HT2 receptors; rat
We distinguished the functions of the different 5-hydroxytryptamine-2 (5-HT2) receptor (5-HT2R) subtypes in the tryptamine-induced 5-HT syndrome in rats using (1) the 5-HT2AR antagonist R93274 (N-[(3-p-fluorophenyl-1-propyl)-4-methyl-4-piperidinyl]-4-amino-5-iodo-2-methoxybenzamide), the 5-HT2A/CR antagonist R99647 (2-(dimethylaminomethyl)2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine), the 5-HT2B/CR antagonist SB-242084 (6-chloro-5-methyl-1-parallel to2-\(2-methyl-3-pyridyl)oxyl-5-pyridyl\carbamoyl\-indoline), and several 5-HT2R antagonists (ketanserin, risperidone, pipamperone and mianserin); and (2) chronic 5-HT2R activation by 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM). In contrast to SB-242084, the selective 5-HT2AR antagonist R93274 as well as the non-selective 5-HT2AR antagonists (1199647, ketanserin, risperidone, pipamperone and mianserin) significantly inhibited tryptamine-induced forepaw treading and tremors, and reversed peripherally mediated cyanosis into hyperaemia; only the 5-HT2A/CR 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(2A)Rs mediate tryptamine-induced forepaw treading and tremors, that peripheral 5-HT(2A)Rs mediate tryptamine-induced cyanosis, and that 5-HT(2C)Rs mediate tryptamine-induced hunched back. Peripheral 5-HT(2A)Rs are more sensitive to desensitization after intermittent treatment with an agonist than central 5-HT(2A)Rs. (C) 2002 Lippincott Williams Wilkins.
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