Effects of acute and long-term treatment with the serotonin1A agonist gepirone on hippocampal afterdischarges in rats

Abstract

We assessed the effects of acute and long-term administration of gepirone, a serotonin1A (5-HT1A) agonist, on hippocampal afterdischarges (ADs) elicited by electrical stimulation in rats. Acute single injection of gepirone at 10 mg/kg produced a significant reduction in the AD threshold, with a significant increase in the AD duration. These facilitatory effects of gepirone were completely blocked by the pretreatment with a 5-HT1A antagonist NAN-190. Following daily administration of gepirone (10 mg/kg/day) for 21 days, rats were challenged with an acute dose of 10 mg/kg of gepirone. These treatment regimens resulted in the lack of the facilitatory effects of acutely injected gepirone, and no significant changes were found in either AD threshold or AD duration. The present results suggest that gepirone facilitates the generation of hippocampal ADs through the activation of 5-HT1A receptors. Long-term treatment with gepirone offset its facilitatory effects, possibly as a result of the desensitization of presynaptic 5-HT autoreceptors.