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Pre‐ and post‐synaptic effects of the 5‐HT 3 agonist 2‐Methyl‐5‐HT on the 5‐HT system in the rat brain
Author(s) -
Haddjeri Nasser,
Blier Pierre
Publication year - 1995
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890200109
Subject(s) - agonist , chemistry , 5 ht receptor , inhibitory postsynaptic potential , antagonist , serotonin , pharmacology , stimulation , endocrinology , medicine , receptor , biochemistry
Microiontophoretic applications of 5‐HT and of the 5‐HT 3 agonist 2‐methyl‐5‐HT produced a current‐dependent suppression of firing activity of both hippocampal (CA 1 and CA 3 ) and cortical neurons in anesthetized rats. Concomitant microiontophoretic applications of the 5‐HT 3 antagonists BRL 46470A and S‐zacopride, as well as their intravenous injection, did not antagonize the inhibitory effect of 5‐HT and 2‐methyl‐5‐HT. In contrast, the 5‐HT 1A antagonist BMY 7378, applied by microiontophoresis or administered intravenously, significantly reduced the inhibitory action of 5‐HT and 2‐methyl‐5‐HT. The firing activity of dorsal raphe 5‐HT neurons was also reduced by 5‐HT, 2‐methyl‐5‐HT and the 5‐HT 1A agonist 8‐OH‐DPAT applied by microiontophoresis. While BRL 46470A (0.1 and 1 mg/kg, i.v.) did not antagonize the inhibitory effect of the three 5‐HT agonists on 5‐HT neuronal firing activity, only that of 8‐OH‐DPAT was attenuated by the 5‐HT 1A antagonist (+) WAY 100135. R‐zacopride significantly reduced the duration of suppression of firing activity of CA 3 pyramidal neurons induced by the electrical stimulation of the ascending 5‐HT pathway, and this reducing effect was prevented by the three 5‐HT 3 /5‐HT 4 antagonists renzapride, S‐zacopride and tropisetron, but not by BRL 46470A. Finally, in in vitro superfusion experiments, both BRL 46470A and S‐zacopride antagonized the enhancing action of 2‐methyld‐HT on the electrically‐evoked release of [ 3 H]‐5‐HT in both rat frontal cortex and hippocampus slices. These findings suggest that, in vivo, the suppressant effect of 2‐methyl‐5‐HT on the firing activity of dorsal hippocampus pyramidal, somatosensory cortical, and dorsal raphe 5‐HT neurons is not mediated by 5‐HT 3 receptors, but rather by 5‐HT 1A receptors. The attenuating effect of R‐zacopride on the effectiveness of the stimulation of the ascending 5‐HT pathway is not mediated by 5‐HT 3 receptors. In contrast, in vitro, the enhancing action of 2‐methyl‐5‐HT on the electrically‐evoked release of [ 3 H]5‐HT in both frontal cortex and hippocampus slices is mediated by 5‐HT 3 receptors. © 1995 Wiley‐Liss, Inc.