Effects of Aripiprazole and Haloperidol on Fos-like Immunoreactivity in the Prefrontal Cortex and Amygdala

OBJECTIVE: Aripiprazole, a dopamine system stabilizer, shows efficacy against both negative symptoms and positive symptoms in patients with schizophrenia. The aim of this study was to investigate the effects of aripiprazole and haloperidol on c-FOS expression in rat brain. METHODS: Aripiprazole (1, 10 and 30 mg/kg, i.p.) and haloperidol (0.1 and 1 mg/kg, i.p.) were administered to adult Male Sprague-Dawley rats. After 2 h of drug or vehicle administration, the rats were killed and their brains were removed and perfused with fixative, then cut into 40 µm slices on a freezing microtome. Brain regions of interest were the medial prefrontal cortex (mPFC), the nucleus accumbens core and shell (NAC-C and NAC-S), the hippocampus (CA1, CA3 and DG), the central amygdala (Ce), the basolateral amygdala (BL) and the temporal cortex (Tc). Immunohistochemistry was performed to label cell bodies containing c-FOS. RESULTS: The administration of aripiprazole at all doses (1, 10 or 30 mg/kg) resulted in greater Fos-like immunoreactivity (FLI) in the investigated brain areas, as compared to the vehicle. Comparable increases in FLI were demonstrated in the NAC-C and NAC-S in response to both aripiprazole and haloperidol treatment. The administration of haloperidol (0.1 or 1 mg/kg) also resulted in greater FLI in the investigated brain areas, except the mPFC, where no changes were observed. In the Ce and BL, a significant increase in Fos-positive neurons was observed only with 0.1 mg/kg of haloperidol. CONCLUSION: Both aripiprazole and haloperidol increased FLI in limbic areas, which are considered important targets of antipsychotic drugs. The differential action of aripiprazole on FLI in the amygdala and mPFC as compared to haloperidol may be a good way to differentiate atypical from typical antipsychotics.