Milnacipran, a serotonin and noradrenaline reuptake inhibitor, suppresses long-term potentiation in the rat hippocampal CA1 field via 5-HT1A receptors and alpha 1-adrenoceptors.
Pharmacological characteristics of a serotonin (5-HT) and noradrenaline reuptake inhibitor (SNRI), milnacipran, in modulation of the synaptic plasticity were investigated. Milnacipran (30 mg/kg, i.p.) suppressed the long-term potentiation (LTP) in the hippocampal CA1 field of anesthetized rats. Milnacipran-induced suppression was reversed by pretreatment with the selective 5-HT1A receptor antagonist WAY 100635 (0.1 mg/kg, i.v.) or the alpha1-adrenoceptor antagonist prazosin (1 and 10 microg/rat, i.c.v.). The alpha2-adrenoceptor antagonist idazoxan (5 mg/kg, i.p.) did not influence the milnacipran-induced synaptic responses. These data suggest that the inhibitory effects of milnacipran on LTP induction are mediated via both 5-HT1A receptors and alpha1-adrenoceptors. In other words, functional interaction between the serotonergic and noradrenergic neuronal systems is involved in alteration of the hippocampal synaptic plasticity, which may be implicated in the SNRI-induced therapeutic effect on psychiatric disorders.
Tachibana
Kaori
K
Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan.
Matsumoto
Machiko
M
Togashi
Hiroko
H
Kojima
Taku
T
Morimoto
Yuji
Y
Kemmotsu
Osamu
O
Yoshioka
Mitsuhiro
M
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D003521:Cyclopropanes / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D000078764:Milnacipran; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D018759:Adrenergic Uptake Inhibitors; D003521:Cyclopropanes; D000078764:Milnacipran; D009638:Norepinephrine; D044282:Receptor, Serotonin, 5-HT1A; D018340:Receptors, Adrenergic, alpha-1; D017367:Selective Serotonin Reuptake Inhibitors