Inhibitory Effect of Ondansetron on Glycine Response of Dissociated Rat Hippocampal Neurons

We examined the effect of ondansetron, an antagonist of type 3 serotonin receptors, on the whole cell response of freshly isolated hippocampal CA1 pyramidal neurons of neonatal and "mature" rats to glycine using the gramicidin perforated patch technique. Ondansetron depressed the current induced by subsaturating concentrations of glycine (IGly) in a concentration-dependent manner. The ondansetron concentration needed to depress IGly induced by 30 microM glycine to half amplitude was 25 microM. Ondansetron (54 microM) shifted the glycine concentration-response curve to the right in a parallel manner, increasing the EC50 for glycine from 40 +/- 3 microM to 70 +/- 5 microM. Ondansetron increased the time constant of activation of IGly without affecting the time constant of deactivation. When examined under current clamp conditions, glycine induced depolarization and hyperpolarization in neonatal and mature neurons, respectively; ondansetron also suppressed these responses to glycine. The data suggest that ondansetron competitively inhibits the glycine receptor.