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Research ArticleArticle

Anxiolytic 5-Hydroxytryptamine1A Agonists Suppress Firing Activity of Dorsal Hippocampus CA1 Pyramidal Neurons through a Postsynaptic Mechanism: Single-Unit Study in Unanesthetized, Unrestrained Rats

Koji Tada, Kimihiro Kasamo, Naoki Ueda, Tadashi Suzuki, Takuya Kojima and Koichi Ishikawa
Journal of Pharmacology and Experimental Therapeutics February 1999, 288 (2) 843-848;
Koji Tada
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Kimihiro Kasamo
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Naoki Ueda
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Tadashi Suzuki
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Takuya Kojima
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Koichi Ishikawa
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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-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.

Footnotes

  • Send reprint requests to: Dr. Koji Tada, Department of Neuropsychiatry, Nihon University School of Medicine, Oyaguchi Kamimachi 30-1, Itabashi Tokyo, 173-8610, Japan.

  • ↵1 Supported by Grant from the Pharmacopsychiatry Research Foundation.

  • Abbreviations:
    5-HT
    5-hydroxytryptamine
    8-OH-DPAT
    8-hydroxy-2-(di-n-propylamino)tetralin
    NAN-190
    1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine
    PCPA
    parachlorphenylalanine
    ANOVA
    analysis of variance
    • Received November 7, 1997.
    • Accepted September 17, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 288 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 288, Issue 2
1 Feb 1999
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Research ArticleArticle

Anxiolytic 5-Hydroxytryptamine1A Agonists Suppress Firing Activity of Dorsal Hippocampus CA1 Pyramidal Neurons through a Postsynaptic Mechanism: Single-Unit Study in Unanesthetized, Unrestrained Rats

Koji Tada, Kimihiro Kasamo, Naoki Ueda, Tadashi Suzuki, Takuya Kojima and Koichi Ishikawa
Journal of Pharmacology and Experimental Therapeutics February 1, 1999, 288 (2) 843-848;

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Research ArticleArticle

Anxiolytic 5-Hydroxytryptamine1A Agonists Suppress Firing Activity of Dorsal Hippocampus CA1 Pyramidal Neurons through a Postsynaptic Mechanism: Single-Unit Study in Unanesthetized, Unrestrained Rats

Koji Tada, Kimihiro Kasamo, Naoki Ueda, Tadashi Suzuki, Takuya Kojima and Koichi Ishikawa
Journal of Pharmacology and Experimental Therapeutics February 1, 1999, 288 (2) 843-848;
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