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.