INHIBITION OF EPILEPTIFORM ACTIVITY BY SEROTONIN IN RAT CA1 NEURONS

This investigation was performed to determine the ability of serotonin in inhibiting bicuculline-induced epileptiform bursts in brain slices of male Sprague-Dawley rats. In all experiments, intracellular record ing techniques were employed on CA1 neurons of the hippocampus. The ne urons were stimulated either directly by the recording electrode or in directly (synaptic stimulation) using a bipolar electrode placed on th e CA2/CA3 region. Serotonin (20 mu M) inhibited the directly evoked bu rsts of action potentials and caused a membrane hyperpolarization and decrease in membrane input resistance in untreated CA1 neurons. In the same experiments, serotonin inhibited the synaptically evoked action potential as well. Additionally, serotonin inhibited epileptiform burs ts induced by single presynaptic stimuli in the presence of bicucullin e. Moreover, in the concomitant presence of serotonin and bicuculline, there was a decrease in the number of spikes in bursts evoked by dire ct stimulation. Inhibition of epileptiform bursts was also achieved wi th the selective 5-HT1A agonist 8-hydroxydipropyl-amino-tetralin (8-OH -DPAT). The presence of the 5-HT3 antagonist MDL 72222 (30 mu M), and the 5-HT2 antagonist ketanserin (3 mu M) did not influence the ability of serotonin to inhibit epileptiform bursts. In the presence of bicuc ulline, the inhibitory action of serotonin, 8-OH-DPAT or the combinati on of serotonin, MDL 72222 and ketanserin, was accompanied by a membra ne hyperpolarization and a decrease in membrane input resistance. To a scertain if serotonin can be applied on other models of epilepsy as we ll, we demonstrate the inhibition of epileptiform activity in the kain ic acid treated brain slice preparation. These results suggest that se rotonin, by activation of the 5-HT1A receptor subtype, may inhibit epi leptiform activity in CA1 neurons of the rat brain slice preparation.