The present study examined the effects of a single and five once daily injections of cocaine on the expression of c-fos mRNA, Fos protein and Fos-related antigens (Fra) in the striatum. A single injection (40 mg/kg, i.p.), which induces locomotion, increased the expression of c-fos mRNA, Fos protein and a 35 kDa Fra. In contrast, five injections (40 mg/kg, i.p.) given once a day, which induces even more behavioral stimulation, diminished the increase in c-fos mRNA and Fos protein expression. However, the cocaine-induced Fra expression was sustained and not reduced after the five injections. The results demonstrate that cocaine-induced expression of the Fos/Fra gene family is dynamic and the profile of gene transcription and translation in the striatum changes when animals are behaviorally more sensitive to cocaine.