Serotonin inhibits epileptiform discharge by activation of 5-HT1A receptors in CA1 pyramidal neurons.
The anti-epileptiform effect of serotonin was characterized in cellular models of epilepsy using electrophysiological recording techniques. In the bicuculline model, both serotonin (20 microM) and its 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 10 microM) completely blocked the epileptiform discharge and caused membrane hyperpolarization and reduction in input resistance. These effects were completely antagonized by the 5-HT1A receptor antagonist N-t-butyl-3(4-[2-methoxyphenyl]piperazin-1-yl)-2-phenyl-propanamid e(WAY 100135) (10 microM). Epileptiform discharge induced by positive current injection was also blocked by serotonin. The presence of WAY 100135 renders serotonin ineffective in the same model. In the bicuculline model, epileptiform discharge blocked by serotonin reappeared and was also intensified when BaCl2 was added to the medium. To rule out the possibility of serotonin-induced hyperpolarization strengthening the inhibitory effect of endogenous Mg2+ on glutamate N-methyl-D-aspartic acid (NMDA) receptor we studied the antiepileptic effect of serotonin in the 0 Mg2+ model. Spontaneous activity and evoked bursts seen with the 0 Mg2+ model were completely blocked by serotonin. WAY 100135 completely antagonized serotonin effects in this model as well. This study provides evidence suggesting that in rat CA1 pyramidal neurons, serotonin can inhibit epileptiform activity in a variety of accepted epilepsy cellular models and that inhibition of epileptiform bursts by serotonin may be mediated by activation of the 5-HT1A receptor subtype.
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; D017609:Barium Compounds / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004594:Electrophysiology; D004827:Epilepsy / Q000473:pathology / Q000503:physiopathology*; D005473:Fluoxetine / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008274:Magnesium / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D017609:Barium Compounds; D001640:Bicuculline; D002712:Chlorides; D005473:Fluoxetine; D018756:GABA Antagonists; D008274:Magnesium; D011985:Receptors, Serotonin; D012701:Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C024986:barium chloride