Endogenous 5-HT tonically inhibits spontaneous firing activity of dorsal hippocampus CA1 pyramidal neurons through stimulation of 5-HT(1A) receptors in quiet awake rats: in vivo electrophysiological evidence.
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-HT(1A) antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xanecarboxamide (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 x 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-HT(2A) antagonist ritanserin (1 mg/kg, i.p.) and a 5-HT(3/4) 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-HT(1A) receptors.
Kasamo
K
K
Departments of Neuropsychiatry, Nihon University School of Medicine, Tokyo, Japan.
Suzuki
T
T
Tada
K
K
Ueda
N
N
Matsuda
E
E
Ishikawa
K
K
Kojima
T
T
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D010134:Fenclonine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D010134:Fenclonine