STIMULANT-MEDIATED C-FOS INDUCTION IN STRIATUM AS A FUNCTION OF AGE, SEX, AND PRENATAL COCAINE EXPOSURE

Induction of the immediate-early gene c-fos by the stimulants cocaine and amphetamine (AMPH) was analyzed by Fos immunocytochemistry at diff erent ages in the brains of prenatally cocaine-treated and control rat s. Cocaine and AMPH induced c-Sos in patches of striatal neurons durin g the first postnatal week, and thereafter produced a progressively mo re homogeneous pattern that was more dense medially. Quantification of Fos-immunoreactive cells in older rats revealed differences related t o sex and prenatal cocaine treatment. Both cocaine and AMPH produced d ose-dependent increases in the number of Fos-immunoreactive cells in s triatum. Prenatal cocaine exposure resulted in increased Fos in males in response to AMPH (2 mg/kg) at P18 and cocaine (10 mg/kg) at 1-2 mon ths. In females, prenatal cocaine treatment resulted in a reduced resp onse to cocaine at 1-2 months. Increased c-fos induction was observed in control females compared to control males in response to low doses of stimulants; no such sex difference was observed in prenatally cocai ne-treated rats. The dopamine D1 antagonist SCH23390 blocked cocaine-m ediated c-fos induction in all groups. The NMDA antagonist MK-801 bloc ked cocaine-mediated c-fos induction in the medial striatum. In female s only, MK-801 pretreatment resulted in a dramatic increase in the num ber of Fos-immunoreactive cells in lateral striatum. These findings in dicate differences in the neural basis of c-fos induction in males and females, and changes in stimulant-mediated c-fos induction resulting from prenatal cocaine exposure. (C) 1998 Elsevier Science B.V. All rig hts reserved.