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 recording techniques were employed on CA1 neurons of the hippocampus. The neurons were stimulated either directly by the recording electrode or indirectly (synaptic stimulation) using a bipolar electrode placed on the CA2/CA3 region. Serotonin (20 microM) inhibited the directly evoked bursts 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 bursts induced by single presynaptic stimuli in the presence of bicuculline. Moreover, in the concomitant presence of serotonin and bicuculline, there was a decrease in the number of spikes in bursts evoked by direct stimulation. Inhibition of epileptiform bursts was also achieved with the selective 5-HT1A agonist 8-hydroxydipropyl-amino-tetralin (8-OH-DPAT). The presence of the 5-HT3 antagonist MDL 72222 (30 microM), and the 5-HT2 antagonist ketanserin (3 microM) did not influence the ability of serotonin to inhibit epileptiform bursts. In the presence of bicuculline, the inhibitory action of serotonin, 8-OH-DPAT or the combination of serotonin, MDL 72222 and ketanserin, was accompanied by a membrane hyperpolarization and a decrease in membrane input resistance. To ascertain if serotonin can be applied on other models of epilepsy, as well, we demonstrate the inhibition of epileptiform activity in the kainic acid treated brain slice preparation.(ABSTRACT TRUNCATED AT 250 WORDS)
Salgado
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Department of Pharmacological and Pharmaceutical Sciences, University of Houston, TX 77204-5515.
Alkadhi
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KA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004558:Electric Stimulation; D004827:Epilepsy / Q000503:physiopathology*; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*
D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001640:Bicuculline