SEROTONIN INHIBITS EPILEPTIFORM DISCHARGE BY ACTIVATION OF 5-HT1A RECEPTORS IN CA1 PYRAMIDAL NEURONS

The anti-epileptiform effect of serotonin was characterized in cellula r models of epilepsy using electrophysiological recording techniques. In the bicuculline model, both serotonin (20 mu M) and its 5-HT1A agon ist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 10 mu M) compl etely blocked the epileptiform discharge and caused membrane hyperpola rization and reduction in input resistance. These effects were complet ely antagonized by the 5-HT1A receptor antagonist oxyphenyl]piperazin- 1-yl)-2-phenyl-propanamide(WAY 100135) (10 mu M). Epileptiform dischar ge 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 se rotonin reappeared and was also intensified when BaCl2 was added to th e medium. To rule out the possibility of serotonin-induced hyperpolari zation strengthening the inhibitory effect of endogenous Mg2+ On gluta mate N-methyl-D-aspartic acid (NMDA) receptor we studied the antiepile ptic effect of serotonin in the 0 Mg2+ model. Spontaneous activity and evoked bursts seen with the 0 Mg2+ model were completely blocked by s erotonin. 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 v ariety of accepted epilepsy cellular models and that inhibition of epi leptiform bursts by serotonin may be mediated by activation of the 5-H T1A receptor subtype. (C) 1998 Elsevier Science Ltd. All rights reserv ed.