Effects of serotonin on induced epileptiform activity in CA1 pyramidal neurons of genetically epilepsy prone rats.
The seizure susceptibility in genetically epilepsy prone rats (GEPRs) is reported to be caused by abnormalities in several neurotransmitter systems including the serotonergic system. Among the reported abnormalities is a decrease in brain serotonin content. Therefore, we examined the effects of exogenous serotonin on brain slices from the severe seizure strain of GEPRs (GEPR-9s). We employed conventional electrophysiological techniques to record from CA1 pyramidal neurons of hippocampi of GEPR-9s. The membrane resting potential and input resistance of the GEPR-9 CA1 pyramidal neurons were not different from those of the Sprague-Dawley rats. Serotonin (20 microM) inhibited the directly and synaptically evoked action potentials in GEPR-9 CA1 neurons, as it did in the Sprague Dawley neurons, but only in some and not all of the neurons tested (blocked the directly evoked potentials in 57% and synaptically evoked potentials in 33.3% of the total neurons). This inhibition was also accompanied by hyperpolarization and reduction of membrane input resistance. In the bicuculline-treated brain slices of the GEPR-9, serotonin inhibited the epileptiform bursts causing concurrent hyperpolarization and reduction in membrane input resistance. The effects of the selective serotonin 5-HT1A receptor agonist, 8-OH-DPAT (20 microM) on GEPR-9 pyramidal CA1 neurons were similar to those of serotonin, except the magnitude of hyperpolarization and reduction of membrane input resistance were less than those produced by serotonin. We conclude that the apparent decrease in sensitivity of the GEPR-9 CA1 pyramidal neurons to serotonin may represent a deficiency of serotonin 5-HT1A receptor.
Salgado-Commissariat
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Department of Pharmacological and Pharmaceutical Sciences University of Houston, TX 77204-5515, USA.
Alkadhi
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004558:Electric Stimulation; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics; D005071:Evoked Potentials / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D066298:In Vitro Techniques; D008297:Male; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D003292:Convulsants; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001640:Bicuculline