Role of 5-HT(2) receptors in the tryptamine-induced 5-HT syndrome in rats.
D Van Oekelen, Anton A. H. P. Megens, Theo Meert, W H M L Luyten, J E Leysen
Behavioural Pharmacology July 2002 DOI: 10.1097/00008877-200207000-00008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | R93274 R99647 SB-242084 ketanserin risperidone pipamperone mianserin DOM |
| Duration | DOM administered intravenously every 48 h for 12 days; assessments at 1, 4, and 7 days after the last DOM pretreatment |
| Topics | Serotonin |
| Key findings | The authors conclude that central 5-HT2A receptors mediate tryptamine-induced forepaw treading and tremors, peripheral 5-HT receptors mediate tryptamine-induced cyanosis, and 5-HT2A receptors mediate hunched back. Intermittent DOM pretreatment did not change central tryptamine responses but reversed peripheral cyanosis to hyperaemia in 75%, 11%, and 20% of rats at 1, 4, and 7 days after the last dose, suggesting peripheral 5-HT2C receptors desensitize more than central 5-HT2A receptors. |
Abstract
We distinguished the functions of the different 5-hydroxytryptamine-2 (5-HT(2)) receptor (5-HT(2)R) subtypes in the tryptamine-induced 5-HT syndrome in rats using (1) the 5-HT(2A)R antagonist R93274 (N-[(3-p-fluorophenyl-1-propyl)-4-methyl-4-piperidinyl]-4-amino-5-iodo-2-methoxybenzamide), the 5-HT(2A/C)R antagonist R99647 (2-(dimethylaminomethyl)2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine), the 5-HT(2B/C)R antagonist SB-242084 (6-chloro-5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-indoline), and several 5-HT(2)R antagonists (ketanserin, risperidone, pipamperone and mianserin); and (2) chronic 5-HT(2)R activation by 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM). In contrast to SB-242084, the selective 5-HT(2A)R antagonist R93274 as well as the non-selective 5-HT(2A)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(2A/C)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(2A)Rs mediate tryptamine-induced forepaw treading and tremors, that peripheral 5-HT Rs mediate tryptamine-induced cyanosis, and that 5-HT(2A)Rs mediate tryptamine-induced hunched back. Peripheral 5-HT(2C)Rs are more sensitive to desensitization after intermittent treatment with an agonist than central 5-HT(2A)Rs.
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