Antipsychotics possessing antidepressive efficacy increase Golf protein in rat striatum

Hideki Taoka, Takashi Hamamura, Shiro Endo, Shinji Miyata, Kishio Toma, Takeshi Ishihara, Shigetoshi Kuroda

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Introduction: 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 α-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. Materials and 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). Results and discussion: 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 G olf may play an important role in the antidepressive effect of antipsychotics. Conclusion: 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.

Original languageEnglish
Pages (from-to)229-235
Number of pages7
JournalPsychopharmacology
Volume201
Issue number2
DOIs
Publication statusPublished - Dec 1 2008

Keywords

  • Antidepressants
  • Antipsychotics
  • Depression
  • Dopamine
  • Dopamine receptor
  • G protein
  • Nucleus accumbens

ASJC Scopus subject areas

  • Pharmacology

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