Dopamine efflux during withdrawal from continuous or intermittent cocaine.

Daily, intermittent, subcutaneous cocaine injections produce sensitization, while the continuous administration of cocaine produces tolerance to the behavioral effects of subsequent cocaine injections. The present experiments examined whether these behavioral differences are related to differences in the ability of cocaine to increase extracellular dopamine. Increases in perfusate DA, in response to different concentrations of cocaine, were measured in caudate-putamen slices obtained from rats withdrawn for 7 days from a 14-day treatment of either continuous or daily subcutaneous cocaine injections. Compared to saline controls, cocaine-induced DA efflux was increased in subjects receiving daily injections and markedly decreased in subjects receiving continuous cocaine. Thus, different temporal patterns of cocaine administration produce dramatically different alterations in DA neurotransmission. Such changes in dopamine release may be related to the withdrawal symptoms experienced by human cocaine abusers.