G(olf) protein levels in rat striatum are increased by chronic antidepressant administration and decreased by olfactory bulbectomy.
There are many studies of the mechanisms of antidepressants; however, most of these studies were conducted on the hippocampus or frontal cortex. In the present study, we hypothesized that the nucleus accumbens and caudate/putamen might be major targets for antidepressant effects. Thus, we focused on G(olf) protein, a stimulant alpha-subunit of G protein that is coupled with the dopamine D1 receptor and specifically expressed in the striatum (nucleus accumbens, caudate/putamen and olfactory tubercle) in the rat brain. We examined the effects of chronic administration of imipramine, fluvoxamine, maprotiline and, as a negative control, cocaine on the level of G(olf) protein in the rat striatum. We also examined the effect of olfactory bulbectomy. Chronic imipramine treatment (10 mg/kg for 2 or 4 weeks) significantly increased the level of G(olf) in the striatum (by 17% or 18%, respectively), although this increase was not apparent after only 1 week of treatment. The time course of these changes corresponded well to that of the clinical efficacy of imipramine. Chronic fluvoxamine and maprotiline treatment (20 mg/kg for 2 weeks) also significantly increased the level of G(olf) (by 9% and 25%, respectively), but cocaine did not alter it significantly. Bulbectomy decreased the G(olf) protein level by 9%. The increases in G(olf) protein after chronic administration of these three different classes of antidepressants and the decrease after bulbectomy suggest that G(olf) protein may play an important role in the antidepressant effect.
Department of Neuropsychiatry, Okayama Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Hideki
H
Taoka
Takashi
T
Hamamura
Shiro
S
Endo
Masahito
M
Miki
Youmei
Y
Lee
Shinji
S
Miyata
Kishio
K
Toma
Takeshi
T
Ishihara
Hidenori
H
Sagara
Yutaka
Y
Gomita
Shigetoshi
S
Kuroda
D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism*; D007099:Imipramine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism*; D009830:Olfactory Bulb / Q000601:surgery*; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D003042:Cocaine; D044385:GTP-Binding Protein alpha Subunits; D007099:Imipramine; D017367:Selective Serotonin Reuptake Inhibitors; C084618:olfactory G protein subunit alpha olf