Differential reinforcing effects of cocaine and GBR-12909: biochemical evidence for divergent neuroadaptive changes in the mesolimbic dopaminergic system

The dopamine (DA) transporter is thought to be the primary mediator of reinforcing effects of cocaine. In the present study, an intravenous drug self-administration procedure, in vitro autoradiography, and HPLC methods were used to investigate possible differences in reinforcing and neuroad-aptive responses to cocaine versus GBR-12909, a selective inhibitor of the DA transporter with a postulated therapeutic use in cocaine abuse. Drug-naive rats readily acquired and subsequently maintained cocaine self-administration behav-ior during 2 hr daily sessions over a prolonged period. In contrast, although GBR-12909 was initially self-administered, both cocaine-naive and cocaine-trained rats failed to maintain self-administration behavior for GBR-12909 over prolonged periods of time. After self-administration responding decreased with GBR-12909, rat