|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1995 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1994 : ¥900,000 (Direct Cost : ¥900,000)
The pharmacological characteristics of neuroleptic were examined in terms of modification of immediate-early gene, c-fos, expression in the rat and macaque monkey forebrain. After subcutaneous injection of nemonapride (0.5,4.0mg/kg) , haloperidol (1mg/kg) , or clozapine (25mg/kg) , Fos-immunocytochemistry was conducted and the distribution of Fos positive neurons were compared. All three antipsychotic drugs enhanced Fos-like immunoreactivity in the rat septum, nucleus accumbens, basal forebrain and hypothalamic regions. A significant increase in the number of immunoreactive cells was observed in the shell of the rat nucleus accumbens after injection of each of the three neuroleptics. On the other hand, there were some differences between the drugs in such forebrain regions as the striatum, globus pallidus, islands of Calleja and amygdala. Specifically, nemonapride and clozapine produced significant increases of Fos-like immunoreactive cells located in the major island of Calleja, central amygdaloid nucleus and paraventricular hypothalamic nucleus. Nemonapride and haloperidol elevated the number of positive cells in the striatum, globus pallidus and the core of the nucleus accumbens, while clozapine did not. Moreover, clozapine treatment alone resulted in a significant increase in the number of Fos-like immunoreactive neurons in the lateral septal nucleus and the medial nucleus of amygdala. Similar observations were made in the primate forebrain regions after an injection of haloperidol. These findings demonstrated that these neuroleptics each have of somewhat different effects on regional c-fos expression which may be related to their different clinical profile.