Environmental modulation of amphetamine-induced c-fos expression in D1 versus D2 striatal neurons

We have reported previously that exposure to environmental novelty enhances the behavioral activating effects of amphetamine and its ability to induce the immediate early gene c-fos in the striatum and in other brain regions. In the present study, we used double in situ hybridization histochemistry to study the effect of amphetamine and/or novelty on c-fos expression in two populations of striatal neurons that preferentially express either D1 or D2 dopamine receptor mRNA. When given intraperitoneally to rats in their home cage, amphetamine (2.0 mg/kg) increased c-fos expression only in D1 neurons. In contrast, when the same dose of amphetamine was administered to rats in a novel environment, c-fos was increased in both D1 and D2 neurons. We conclude that the neural populations engaged by amphetamine vary as a function of the circumstances surrounding its administration.