Impact of self-administered cocaine and cocaine cues on extracellular dopamine in mesolimbic and sensorimotor striatum in rhesus monkeys

Studies were conducted to determine the impact of self-administered cocaine on extracellular striatal dopamine in four rhesus monkeys. The extent to w hich external cue conditioning contributed to the effects of cocaine and wh ether there is activation of striatal dopaminergic neurotransmission during drug-seeking behavior was also examined. Microdialysis measurements were m ade at 2 min intervals in sensorimotor (dorsolateral) and mesolimbic (centr al and ventromedial) striatum. A fixed-ratio schedule of reinforcement was used, with cocaine availability signaled by a visual cue. Studies examined the effects of cocaine or cocaine cues against a drug-free baseline. Large (fivefold to eightfold) increases in extracellular dopamine after a self-ad ministered infusion of 0.5 mg/kg cocaine were quite rapid and matched the t ime course of reported subjective effects in human laboratory studies. To d etermine if conditioning to external cues contributed to the cocaine-induce d increases, saline was substituted for cocaine in the infusion, leaving al l other visual and auditory stimuli unchanged. No increase in extracellular dopamine in either sensorimotor or mesolimbic striatal subdivisions was ob served. Extracellular dopamine during extended periods of drug-seeking beha vior triggered by a visual cue was determined in both central and ventromed ial striatum. This procedure also did not result in any measurable changes in extracellular dopamine. These studies demonstrate rapid and pronounced p harmacological actions of self-administered cocaine. No apparent conditione d component of those actions was associated with external environmental cue s, suggesting that cues that trigger drug-seeking behavior in nonhuman prim ates do not cause conditioned increases in mesolimbic striatal dopamine.