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 different ages in the brains of prenatally cocaine-treated and control rats. Cocaine and AMPH induced c-fos in patches of striatal neurons during the first postnatal week, and thereafter produced a progressively more homogeneous pattern that was more dense medially. Quantification of Fos-immunoreactive cells in older rats revealed differences related to sex and prenatal cocaine treatment. Both cocaine and AMPH produced dose-dependent increases in the number of Fos-immunoreactive cells in striatum. 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 months. In females, prenatal cocaine treatment resulted in a reduced response 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 cocaine-treated rats. The dopamine D1 antagonist SCH23390 blocked cocaine-mediated c-fos induction in all groups. The NMDA antagonist MK-801 blocked cocaine-mediated c-fos induction in the medial striatum. In females only, MK-801 pretreatment resulted in a dramatic increase in the number of Fos-immunoreactive cells in lateral striatum. These findings indicate 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.
Snyder-Keller
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Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany, NY 12201, USA. snykell@wadsworth.org
Keller
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RW
D000375:Aging / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013268:Stimulation, Chemical
D001552:Benzazepines; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D000661:Amphetamine; D003042:Cocaine