Ipsapirone depresses neuronal activity in the dorsal raphe nucleus and the hippocampal formation

Ipsapirone, a putative, novel anxiolytic with a high affinity for 5-HT1A binding sites, suppressed neuronal activity in both the dorsal raphe nucleus and hippocampal formation of urethane-anesthetized rats. In the hippocampus, dentate granule cells matched the responsiveness of dorsal raphe serotonin neurons, the median effective dose for 50% inhibition being 125.0 micrograms/kg in both areas. In contrast, the responses of CA1 pyramidal cells were related directly to baseline firing rates. Slow-firing neurons, for example, were inhibited by 31.3 micrograms/kg and fast-firing cells were unresponsive even up to a dose of 500.0 micrograms/kg. These results indicate a potent effect of ipsapirone on neuronal activity in sites with a high density of 5-HT1A receptors.