GBR 12909 fails to antagonize cocaine-induced elevation of dopamine in striatal slices.

The effects of cocaine and 1-(2-bis (4-fluorophenyl)methoxy)-ethyl)-4-(3-phenyl-propyl) piperazine (GBR 12909), alone and together, on [3H] dopamine efflux from superfused rat striatal slices was studied. Both drugs elicited a concentration-dependent increase in spontaneous [3H]dopamine efflux. GBR 12909 when added together with cocaine, had no effect on cocaine-induced [3H] dopamine efflux. It was also determined that GBR 12909 was fully efficacious as an inhibitor of synaptosomal [3H] dopamine uptake and, whether administered in vitro or in vivo, acted in a manner consistent with competitive inhibition. These data are discussed in reference to the recent report that i.p. administration of GBR 12909 antagonized the effect of cocaine on extracellular striatal dopamine levels when infused directly through the dialysis probe, perhaps by acting as a 'partial agonist' at the inhibitory site on the dopamine transporter (Rothman et al., 1991 Pharmacol. Biochem. Behav. 40, 387-397).