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 μM) and its 5-HT_1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 10 μM) completely blocked the epileptiform discharge and caused membrane hyperpolarization and reduction in input resistance. These effects were completely antagonized by the 5-HT_1A receptor antagonist N-t-butyl-3(4-[2-methoxyphenyl]piperazin-1-yl)-2-phenyl-propanamide (WAY 100135) (10 μM). 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 OMg²⁺ 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-HT_1A receptor subtype.