FOS-like Immunoreactivity in Rat Brain Induced by Haloperidol, Clozapine, and Haloperidol Combined with Serotonergic Agents

Kim, Kwang Soo; Bahk, Won Myong; Sei, Sang Won

Abstract

OBJECTIVES
The purpose of this study was to investigate the differences between potential neuroanatomical sites of action of(1) a typical antipsychotic drug (haloperidol), (2) an atypical antipsychotic drug (clozapine), and (3) three combinations of both haloperidol and serotonergic agents (haloperidol+buspirone, haloperidol+cyproheptadine, haloperidol+fluoxetine) by comparing their effects on c-fos expression in the rat brain.
METHODS
Twenty-four Wistar rats of male sex, weighing 300-450 g, were divided into 6 groups according to the type of the agents tested [vehicle (0.14 M acetic acid 1 ml/kg), haloperidol (1.0 mg/kg), clozapine (20 mg/kg), haloperidol+buspirone (1.0 mg/kg+1.0 mg/kg), haloperidol+cyproheptadine (1.0 mg/kg+1.0 mg/kg), haloperidol+fluoxetine (1.0 mg/kg+0.25 mg/kg)]. The brain of variously treated rat was examined 2 hours after subcutaneousely injection in the neck. The brain was removed immediately after perfusion with 4% paraformaldehyde and placed in a fresh fixative of the same solution. After 12-hr fixation, brain sections (30 mum) of the areas including the medial prefrontal cortex, nucleus accumbens, and lateral striatum were stained by Fos immunohistochemistry, and subjected to light microscopic analytical observations.
RESULTS
1) The number of Fos-positive neurons in the medial prefrontal cortex was significantly increased in the clozapine, haloperidol+buspirone, haloperidol+cyproheptadine, and haloperidol+fluoxetine treated groups than in the control group (p<0.05). But, the haloperidol treated group shows no significant difference. 2) The number of Fos-positive neurons in the nucleus accumbens was significantly increased in the haloperidol clozapine, haloperidol+buspirone, haloperidol+cyproheptadine, haloperidol+fluoxetine treated groups than in the control group (p<0.05). 3) The number of Fos-positive neurons in the lateral striatum was significantly increased in the haloperidol, haloperidol+buspirone, haloperidol+cyproheptadine, haloperidol+fluoxetine treated groups than in the control group (p<0.05). But, the clozapine treated group shows no significant difference.
CONCLUSION
These results suggest that differential expression of c-fos in rat brain induced by haloperidol, clozapine, and haloperidol combined serotonergic agents is associated with their clinical and pharmacological differences.