[Effect of fluvoxamine, a new antidepressant drug, on monoamine dynamics in the rat cerebral limbic system and its pharmacological characteristic].
The effect of fluvoxamine (FLU) on the amine dynamics in serotonergic, noradrenergic or dopaminergic nervous systems in the rat cerebral limbic system was investigated, with reference to the pharmacological characteristics of FLU. Following single oral administration of 30 and/or 60 mg/kg FLU, significant decreases in the 5-hydroxyindole-3-acetic acid (5-HIAA)/serotonin (5-HT) ratios in the amygdala and hippocampus and the 4-hydroxy-3-methoxyphenylglycol (MHPG)/norepinephrine (NE) ratio in the amygdala were produced. FLU at 15 mg/kg, p.o. also caused a significant increase in MHPG/NE ratio in the hippocampus. On the other hand, imipramine (IMI) at 30 mg/kg, p.o. induced significant decreases in 5-HIAA/5-HT ratio in the hippocampus, MHPG/NE ratios in the amygdala and hippocampus, and 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) ratios in the amygdala, hippocampus and septum. The 5-HIAA/5-HT ratios in the amygdala and hippocampus and the MHPG/NE ratio in the septum were significantly decreased after repeated oral administration of 30 mg/kg FLU twice daily for 14 days, but the MHPG/NE ratio in the amygdala was increased. In the septum, DOPAC/DA ratio was significantly decreased following repeated administration of IMI at 30 mg/kg, p.o. These findings suggest that FLU inhibits 5-HT turnover in the amygdala and hippocampus as a result of the interference with the neuronal re-uptake mechanism for 5-HT. Also, FLU has an effect on NE turnover in the cerebral limbic system, and the effect may appear in connection with a change in the interaction of nervous systems.
Baba
T
T
Department of Pharmacology, Tokyo Medical College, Japan.
Takeda
H
H
Lee
J W
JW
Takada
K
K
Shibuya
T
T
D000284:Administration, Oral; D000679:Amygdala / Q000378:metabolism; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D016666:Fluvoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism
D015306:Biogenic Monoamines; D012701:Serotonin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D016666:Fluvoxamine; D007099:Imipramine; D009638:Norepinephrine