TY - JOUR T1 - Anxiolytic 5-Hydroxytryptamine<sub>1A</sub> Agonists Suppress Firing Activity of Dorsal Hippocampus CA1 Pyramidal Neurons through a Postsynaptic Mechanism: Single-Unit Study in Unanesthetized, Unrestrained Rats JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 843 LP - 848 VL - 288 IS - 2 AU - Koji Tada AU - Kimihiro Kasamo AU - Naoki Ueda AU - Tadashi Suzuki AU - Takuya Kojima AU - Koichi Ishikawa Y1 - 1999/02/01 UR - http://jpet.aspetjournals.org/content/288/2/843.abstract N2 - 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-HT1Aagonists on pyramidal cell activity in the hippocampus. We examined the effects of 5-HT1A agonists on the spontaneous firing rate of hippocampal CA1 pyramidal neurons in unanesthetized, unrestrained rats. Systemic administration of selective 5-HT1A agonists, 8-hydroxy-2-(di-n-propylamino)tetralin, buspirone, ipsapirone, and flesinoxan produced a dose-dependent inhibition of neuronal activity. Putative 5-HT1A 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-HT1A agonists in awake rats is mediated by postsynaptic 5-HT1A receptors located on pyramidal neurons. The American Society for Pharmacology and Experimental Therapeutics ER -