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Original Article
Neuropsychopharmacology (2001) 24 141-151.10.1038/sj.npp.1395589

Endogenous 5-HT Tonically Inhibits Spontaneous Firing Activity of Dorsal Hippocampus CA1 Pyramidal Neurons Through Stimulation of 5-HT1A Receptors in Quiet Awake Rats: In Vivo Electrophysiological Evidence

Kimihiro Kasamo1 MD, Ph.D, Tadashi Suzuki1 MD, Ph.D, Koji Tada1 MD, Ph.D, Naoki Ueda1 MD, Ph.D, Emi Matsuda1 MD, Koichi Ishikawa2 MD, Ph.D and Takuya Kojima1 MD, Ph.D
1Departments of Neuropsychiatry, Nihon University School of Medicine, Tokyo, Japan
2Departments of Pharmacology, Nihon University School of Medicine, Tokyo, Japan

Correspondence: Dr Kimihiro Kasamo, Department of Neuropsychiatry, Nihon University School of Medicine, Oyaguchi Kamimachi 30-1, Itabashi, Tokyo 173-8610, Japan

ABSTRACT

The present study was performed to examine an overall effect of endogenous serotonin (5-HT) on the spontaneous firing activity of the dorsal hippocampus CA1 pyramidal neurons in quiet awake rats. A selective 5-HT1A antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY-100635: 0.03-0.2 mg/kg, s.c.) significantly increased the firing activity. A depletion of 5-HT with parachlorophenylalanine (PCPA: 500 mg/kg/day ´ 3 days) completely abolished this increasing effect of WAY-100635. The baseline spike frequency of the PCPA-treated rats (3.90 ± 0.39 Hz) was significantly higher than that of the vehicle-treated rats (2.09 ± 0.19 Hz). A 5-HT2A antagonist ritanserin (1 mg/kg, i.p.) and a 5-HT3/4 antagonist 2-methoxy-4-amino-5-chloro benzoic acid 2-(diethylamino) ethyl ester (SDZ-205557: 3 mg/kg, s.c.) did not modify the firing activity and the increasing effect of WAY-100635. These results suggest that, in quiet awake rats, endogenous 5-HT would tonically inhibit the spontaneous firing activity of the CA1 pyramidal neurons mainly through stimulating 5-HT1A receptors.

Keywords: Endogenous serotonin (5-HT); Awake; Unrestrained; CA1 pyramidal neuron, Firing activity; Tonic inhibition, 5-HT1A receptor
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