The role of 5-HT₇ receptors in the control of seizures

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• 作者：Danka Perič ; ić ; ; Dubravka &#x160 ; vob &#x160 ; trac
• 关键词：SB-269970 ; (R)-3-(2-(4-methylpiperidin-1-yl)ethyl)pyrrolidine-1-sulfonyl)phenol ; Ritanserin ; 5-CT (5-carboxamidotryptamine) ; 5-HT₇ receptor ; Picrotoxin-induced convulsion ; Swim stress
• 刊名：Brain Research
• 出版年：2007
• 出版时间：13 April 2007
• 年：2007
• 卷：1141
• 期：Complete
• 页码：48-55
• 全文大小：1043 K

文摘

Serotonin exerts its effects via at least 14 different receptor subtypes, but the role of only a few of them has been studied in relation to the control of seizures. A negative role of 5-HT₇ receptors has recently been proposed. To evaluate further in unstressed and stressed animals the possible role of this receptor subtype in the control of brain excitability, we treated mice with antagonists and agonists of these receptors prior to exposure to swim stress and the intravenous infusion of picrotoxin, a non-competitive GABA_A receptor antagonist. In accordance with the previous studies, swim stress increased the doses of picrotoxin producing two convulsant signs (running/bouncing clonus, tonic hindlimb extension) and death, i.e., swim stress increased the seizure threshold for picrotoxin. SB-269970 (10–30 mg/kg ip), a selective antagonist of 5-HT₇ receptors, and ritanserin (1 mg/kg ip), a nonselective 5-HT _2/7 antagonist, failed to affect, while 5-carboxamidotryptamine (5-CT), a potent 5-HT _1/7 receptor agonist, increased in unstressed and swim-stressed mice the doses of picrotoxin producing convulsions and death. The anticonvulsant effect obtained with 5-CT 0.5 mg/kg was not greater than that obtained with 0.1 mg/kg. The 5-CT (0.1 mg/kg ip)-induced increase of the seizure threshold for picrotoxin in stressed mice was abolished with SB-269970 (10 mg/kg), but not with WAY-100635 (0.3 mg/kg), a selective antagonist of 5-HT_1A receptors, suggesting that the anticonvulsant effect of 5-CT against convulsions produced by picrotoxin was achieved via 5-HT₇ receptors. The results suggest a positive role of 5-HT₇ receptors in the control of seizures.