5-HT1A receptor agonists modify epileptic seizures in three experimental models in rats.
The effects of two serotonergic (5-HT1A) receptor agonists (8-OH-DPAT; 0.01, 0.1, 0.3, 1 mg/kg, s.c., and Indorenate; 1, 3, 10 mg/kg, i.p.) were evaluated in three type of seizures in male Wistar rats: clonic-tonic convulsions induced by pentylenetetrazol (PTZ, 60 mg/kg, i.p.), status epilepticus (SE) of limbic seizures produced by kainic acid (KA, 10 mg/kg, i.p.) and tonic-clonic seizures by amygdala kindling. 8-OH-DPAT decreased the incidence of tonic seizures and the mortality rate induced by PTZ. Indorenate increased the latency to the PTZ-induced seizures and decreased the percentage of rats showing tonic extension and death. Concerning KA, 8-OH-DPAT augmented the latency and reduced the frequency of wet-dog shake (WDS) and generalized seizure (GS). At high doses it diminished the occurrence and delayed the establishment of SE. Indorenate augmented the latency to WDS, GS and SE, and diminished the number of GS. 8-OH-DPAT and Indorenate did not alter the expression of kindled seizures. However, Indorenate enhanced the refractoriness to subsequent seizures during the postictal depression. Some effects induced by 8-OH-DPAT and Indorenate on seizures evaluated and postictal depression were fully or partially blocked by WAY100635. These results suggest that 5-HT1A receptor agonists modify epileptic activity depending on the type of seizure.
Departamento de Farmacobiología Centro de Investigacion y de Estudios Avanzados, Czda. Tenorios 235. Col. Granjas Coapa 14330 Mexico DF, Mexico.
María-Leonor
ML
López-Meraz
María-Eva
ME
González-Trujano
Leticia
L
Neri-Bazán
Enrique
E
Hong
Luisa Lilia
LL
Rocha
D008735:5-Methoxytryptamine / Q000031:analogs & derivatives / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000679:Amygdala; D000818:Animals; D000927:Anticonvulsants; D003292:Convulsants; D004305:Dose-Response Relationship, Drug; D017029:Epilepsy, Complex Partial / Q000517:prevention & control; D004829:Epilepsy, Generalized / Q000188:drug therapy / Q000503:physiopathology; D004830:Epilepsy, Tonic-Clonic / Q000188:drug therapy / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid; D007696:Kindling, Neurologic; D008297:Male; D010433:Pentylenetetrazole; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D012640:Seizures / Q000188:drug therapy*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013226:Status Epilepticus / Q000139:chemically induced / Q000517:prevention & control
D000927:Anticonvulsants; D003292:Convulsants; D018690:Excitatory Amino Acid Agonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D008735:5-Methoxytryptamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C033600:indorenate; D007608:Kainic Acid; D010433:Pentylenetetrazole