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Eur J Pharmacol. 2005 Dec 19;527(1-3):105-10. Epub 2005 Nov 28.

Stimulation of 5-HT 1A receptors increases the seizure threshold for picrotoxin in mice.

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Ruder Bosković Institute, Laboratory for Molecular Neuropharmacology, Division of Molecular Medicine, P.O.B. 180, 10002 Zagreb, Croatia.


To evaluate the possible role of 5-HT 1A and 5-HT 2A receptors in the anticonvulsant effect of swim stress, mice were pre-treated with agonists and antagonists of these receptors prior to exposure to stress and the intravenous infusion of picrotoxin. 8-OH-DPAT ((+/-)-8-hydroxy-2-(di-n-propylamino) tetralin) and WAY-100635 (a selective agonist and antagonist of 5-HT 1A receptors), DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) and ketanserin (a 5-HT 2A/2C receptor agonist and antagonist) were used. Results demonstrated that 1 and 3 mg/kg of 8-OH-DPAT increased the doses of picrotoxin producing running/bouncing clonus, tonic hindlimb extension and death in stressed and unstressed mice, respectively. Pre-treatment with WAY (0.3 mg/kg) prevented the effect of 8-OH-DPAT (3 mg/kg). DOI (2.5 mg/kg) and ketanserin (1 mg/kg) failed to affect the seizure threshold for picrotoxin. The results show that stimulation of 5-HT 1A receptors exerts anticonvulsant actions in stressed and unstressed mice, while stimulation of 5-HT 2A/2C receptors does not interfere with the effect of stress on picrotoxin-induced convulsions.

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