흰쥐 뇌에서 항정신병약물이 C-fos 발현에 미치는 영향

The Effects of Antipsychotics on c-fos Expression in Rat Brain

Objects : To investigate characteristic effects of antipsychotics in brain, the authors studied some potential neuroantatomical differences in the actions of typical antipsychotics (chlorpromazine, haloperidol), atypical antipsychotics(clozapine, risperidone) and selective dopamine D l receptor antagonist(SCH 23390) by comparing their effects on c-fos expression in the rat brain. Methods : Fifty-two rats, weighing 300-450g, were divided into 13 groups according to injection agents [water, vehicle, chlorpromazine, haloperidol, clozapine, risperidone, SCH 23390]. Each brain was removed immediately after perfusion and placed in fresh fixative. After postfixative period, the brain sections(area of the medial prefrontal cortex, nucleus accumbens, medial striatum, lateral striatum and lateral septal nucleus) were stained by c-fos immunohistochemistry. Results ： 1) Chlorpromazine(50mg/kg), clozapine(20mg/kg, 30mg/kg) and risperidone increased the number of Fos-postive neurons in the medial prefrontal cortex than control subjects(p < .01). 2) Chlorpromazine, haloperidol, clozapine and risperidone( 1 mg/kg) increased but SCH 23390 decreased the number of Fos-postive neurons in the nucleus accumbens than control subjects(p < .01). 3) Chlorpromazine, haloperidol and risperidone increased the number of Fos-positive neurons in the striatum, especially in the lateral striatum than control subjects(p〈 .01), but clozapine increased much less than chlorpromazine, haloperidol and risperidone. SCH 23390 decreased the number of Fos-positive neurons in the medial striatum than control subjects(p〈 . 05). 4) Chlorpromazine, haloperidol, clozapine and risperidone increased the number of Fos-postive neurons in the lateral septal nucleus than control subjects(p〈 .01). Conclusion ： These results support that clozapine and risperidone s unique therapeutic actions on negative symptoms with a low incidence of extrapyramidal side effects in schizophrenia may be related to their distinctive effects in regions such as the medial prefrontal cortex and lateral striatum.