Acute and chronic dopamine dynamics in a nonhuman primate model of recreational cocaine use

Using a model of recreational cocaine consumption, we have determined in fo ur rhesus monkeys the impact of self-administered cocaine on mesolimbic and sensorimotor striatal dopaminergic neurotransmission. The effects of cocai ne repeated within a self-administration session and across multiple sessio ns over a 6 month period were determined by the use of fixed-ratio self-adm inistration and microdialysis procedures. The exposure to cocaine was modes t, with at most two 0.5 mg/kg infusions permitted in each weekly session. W ithin a cocaine self-administration session, acute tolerance to the ability of cocaine to elevate extracellular striatal dopamine was observed. Over a period of 6 months of repeated self-administration, there was a significan t increase in the impact of a fixed dose on extracellular dopamine, indicat ing that neurochemical sensitization to the effects of self-administered co caine occurs in primates. A pronounced dopaminergic response to noncontinge nt cocaine was also observed, with no increases in extracellular dopamine i n response to an unexpected saline substitution, indicating that the neuroc hemical response to self-administered cocaine is primarily caused by direct pharmacological effects of the drug rather than by conditioning to externa l environmental cues. These results highlight the contrast in time-dependen t changes in neurochemical responsiveness to cocaine, depending on whether within-session or between-session comparisons are made. They also demonstra te that recreational levels of cocaine consumption can result in neurochemi cal sensitization, an enduring change in brain function that may contribute to addiction.