Amisulpride and Haloperidol-Induced c-Fos Expression in the Rat Brain

Park, Chul Hyun; Huang, Guang Biao; Zhao, Tong; Chung, Young Chul

Abstract

OBJECTIVE
Amisulpride, a D2/D3 dopamine receptor blocker, shows efficacy against both negative symptoms in a low dose range and positive symptoms in a high dose range. The aim of the study was to investigate the effects of amisulpride and haloperidol on the c-Fos expression in rat brain.
METHODS
Amisulpride (0.5, 5 and 50 mg/kg, ip) and haloperidol (0.1 and 1 mg/kg, ip) were administered to adult male Sprague-Dawley rats. Two hours after drugs or vehicle administration, rats were killed and their brains were perfused with fixative. The brains were cut at 40 microm on a freezing microtome. Brain regions of interest were medial prefrontal cortex (mPFC), nucleus accumbens core and shell, hippocampus (CA1, CA3 and dentate gyrus), central amygdala nucleus, basolateral amygdala nucleus and temporal cortex. To label cell bodies containing c-Fos, immunohistochemistry was performed.
RESULTS
The administration of amisulpride in all doses (0.5, 5 and 50 mg/kg) demonstrated greater c-Fos expressions in all of the investigated brain areas, compared to the vehicle. Interestingly, low doses (0.5 mg/kg) of amisulpride showed greater c-Fos expression in the mPFC than high dose of amisulpride (50 mg/kg). The administration of haloperidol (0.1 and 1 mg/kg) also demonstrated greater c-Fos expressions in all of the investigated brain areas except mPFC, compared to the vehicle.
CONCLUSION
Both amisulpride and haloperidol increased c-Fos expressions in limbic areas which are considered as the sites of antipsychotic effects. The findings that lower doses of amisulpride increased greater c-Fos expressions in the mPFC, may explain the beneficial effects of low dose of amisulpride on the negative or depressive symptoms in patients with schizophrenia.