Abstract

Recent behavioral studies indicate that conditioned fear response to contextual stimuli is reduced effectively by anxiolytic 5-hydroxytryptame (5-HT)_1A agonists. Since the hippocampus seems to play an essential role in associative fear memories evoked by context, it is important to assess the effect of 5-HT_1Aagonists on pyramidal cell activity in the hippocampus. We examined the effects of 5-HT_1A agonists on the spontaneous firing rate of hippocampal CA1 pyramidal neurons in unanesthetized, unrestrained rats. Systemic administration of selective 5-HT_1A agonists, 8-hydroxy-2-(di-n-propylamino)tetralin, buspirone, ipsapirone, and flesinoxan produced a dose-dependent inhibition of neuronal activity. Putative 5-HT_1A antagonists NAN-190 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine and (−)-pindolol did not change neuronal activity of CA1 pyramidal neurons. The suppression of neuronal activity by buspirone was antagonized by NAN-190 but not by (−)-pindolol. Lack of antagonistic activity of (−)-pindolol for the suppression of pyramidal neurons via a postsynaptic mechanism is consistent with the results of recent electrophysiological experiments in anesthetized rats. Pretreatment with parachlorphenylalanine did not change the spontaneous firing rates of hippocampal CA1 pyramidal neurons or abolish the suppressant effects of buspirone on these neurons. Taken together, the present results strongly suggest that suppression of the hippocampal CA1 pyramidal neuronal activity by anxiolytic 5-HT_1A agonists in awake rats is mediated by postsynaptic 5-HT_1A receptors located on pyramidal neurons.