Stimulation of 5-HT 1A receptors increases the seizure threshold for picrotoxin in mice.
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.
Pericić
Danka
D
Ruder Bosković Institute, Laboratory for Molecular Neuropharmacology, Division of Molecular Medicine, P.O.B. 180, 10002 Zagreb, Croatia. pericic@irb.hr
Lazić
Josipa
J
Jazvinsćak Jembrek
Maja
M
Svob Strac
Dubravka
D
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology / Q000627:therapeutic use; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D010852:Picrotoxin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013312:Stress, Physiological / Q000209:etiology; D013550:Swimming
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000662:Amphetamines; D007650:Ketanserin; D010852:Picrotoxin; D010879:Piperazines; D011725:Pyridines; D044282:Receptor, Serotonin, 5-HT1A; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine