CHRONIC REPEATED COCAINE ADMINISTRATION INCREASES DOPAMINE D-1 RECEPTOR-MEDIATED SIGNAL-TRANSDUCTION

Alteration in dopamine D-1 receptor-mediated signal transduction follo wing repeated cocaine administration was investigated. Male Fischer ra ts were administered saline or cocaine HCl (15 mg/kg, i.p.) three time s daily at 1-h intervals for 1, 7, or 14 days. Stimulation of adenylyl cyclase activity by dopamine and the selective dopamine D-1 receptor agonist, /-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4, 5-tetra-hy dro-1H-3-benzazepine hydrobromide (SKF 82958), was significantly great er in the nucleus accumbens and caudate putamen of animals injected wi th cocaine for 14 days compared with control animals, but was unchange d in animals administered cocaine for 1 or 7 days. These results sugge st that dopamine D-1 receptor signal transduction in the nucleus accum bens and caudate putamen is enhanced following chronic repeated admini stration of cocaine.