Antipsychotics possessing antidepressive efficacy increase Golf protein in rat striatum.
BACKGROUND
Recently, second-generation antipsychotics (SGAs) have been widely used in the treatment of mood disorders. However, the mechanisms of the antidepressant effect of SGAs remain unclear. We proposed that Golf protein, a stimulant alpha-subunit of G protein coupled with the dopamine D1 receptor, might a play the key role in the antidepressive effect of antidepressants. To clarify the relationship between Golf protein and the antidepressive effects of antipsychotics, we examined the effects of chronic treatment with several antipsychotics on the level of Golf protein in the rat striatum.


METHODS
Male Wistar rats were treated with one of several antipsychotics for 2 weeks: olanzapine (2, 5, or 10 mg/kg), sulpiride (5, 10, or 50 mg/kg), amisulpride (3, 10, or 20 mg/kg), risperidone (0.2 or 2 mg/kg), haloperidol (0.3 or 3 mg/kg), or clozapine (2 or 10 mg/kg).


CONCLUSIONS
Olanzapine (5 mg/kg), sulpiride (5, or 10 mg/kg), and amisulpride (10 mg/kg) treatments significantly increased the level of Golf protein, but there was no increase with administration of higher doses of these three antipsychotics. Risperidone, haloperidol, and clozapine treatment did not change the level of Golf protein at any dose. In this study, all antipsychotics that have antidepressive effects increased Golf protein. This suggests that an increase in Golf may play an important role in the antidepressive effect of antipsychotics.


CONCLUSIONS
We postulate that the increase in Golf protein levels result in an increase the proportion of D1 receptors in the high-affinity state and that augmentation of the dopaminergic system exerts the antidepressant effect.
Taoka
Hideki
H
Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, and Okayama Red Cross General Hospital, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan.
Hamamura
Takashi
T
Endo
Shiro
S
Miyata
Shinji
S
Toma
Kishio
K
Ishihara
Takeshi
T
Kuroda
Shigetoshi
S
D000077582:Amisulpride; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000494:pharmacology / Q000627:therapeutic use; D015153:Blotting, Western; D003024:Clozapine / Q000008:administration & dosage; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D044385:GTP-Binding Protein alpha Subunits / Q000737:chemistry / Q000378:metabolism*; D006220:Haloperidol / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D008297:Male; D000077152:Olanzapine; D051381:Rats; D017208:Rats, Wistar; D018967:Risperidone / Q000008:administration & dosage; D013469:Sulpiride / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors
D014150:Antipsychotic Agents; D044385:GTP-Binding Protein alpha Subunits; C084618:olfactory G protein subunit alpha olf; D001569:Benzodiazepines; D013469:Sulpiride; D000077582:Amisulpride; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine
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