| Budget Amount *help |
¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1990: ¥4,400,000 (Direct Cost: ¥4,400,000)
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| Research Abstract |
The proto-oncogene c-fos encodes phosphoprotein Fos and can be activated in the central nervous system by a variety of physiological and pharmacological treatments. Recently,it has been reported that haloperidol significantly increase neuronal Fos- immunoreactivity in the strdelatum and other forebrain regions (Robertson & Fibiger, 1991). To further study the neuronal system that might mediate the therapeutic action of neuroleptics,the distribution of Fos-immunoreactive neurons were investigated in the rat forebrain after subcutaneous injection of haloperidol (1mg/kg) and clozapine (30 mg/kg),the latter an atypical neuroleptic. A significant increase in the number of Fos-immunoreactive neurons were observed in the strdelatum, nucleus accumbens, lateral septal nucleus, central amygdaloid nucleus,paraventricular thalamic nucleus and other diencephalic nuclei after acute haloperidol treatment. An acute administration of clozapine also produced increase in the number Fos- positive neurons in the medial prefrontal cortex,lateral septal nucleus,nucleus accumbens and other forebrain regions except the strdelatum. These results indicate that the difference in therapeutic action of neuroleptics may be related to its distinctive pattern of c-fos activation observed in the present investigation. Using another series of rats and monkeys treated with haloperidol or clozapine, a molecular biological technique using in situ hybridization histochemistry was employed to study the effect of neuroleptics on mRNA expressions of enkephalin. Quantitative analysis revealed increased enkephalin mRNA expressison in the medium-sized cells of the strdelatum after chronic administration of neuroleptics. These findings provided detailed informations on the effect of dopamine transmission in the forebrain regions.
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