Alteration in dopamine D1 receptor-mediated signal transduction following repeated cocaine administration was investigated. Male Fischer rats were administered saline or cocaine HC1 (15 mg/kg, i.p.) three times daily at 1-h intervals for 1, 7, or 14 days. Stimulation of adenylyl cyclase activity by dopamine and the selective dopamine D1 receptor agonist, (+/-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2, 3,4,5-tetra-hydro-1 H-3-benzazepine hydrobromide (SKF 82958), was significantly greater in the nucleus accumbens and caudate putamen of animals injected with cocaine for 14 days compared with control animals, but was unchanged in animals administered cocaine for 1 or 7 days. These results suggest that dopamine D1 receptor signal transduction in the nucleus accumbens and caudate putamen is enhanced following chronic repeated administration of cocaine.