Cocaine-induced changes in extracellular dopamine determined by microdialysis in awake squirrel monkeys

Rationale: The behavioral effects of cocaine have been linked to brain dopa mine systems. Extending the findings to neurochemical studies in the squirr el monkey would enhance our understanding of the behavioral pharmacology of cocaine in nonhuman primates. Objectives: The present studies characterize d the effects of cocaine and the selective dopamine uptake inhibitor GBR 12 909 on extracellular dopamine in the caudate nucleus of awake squirrel monk eys through microdialysis experiments. Methods: Guide cannulae were implant ed in the caudate nucleus of four monkeys using a stereotaxic apparatus and coordinates obtained from a standard squirrel monkey brain atlas. Accurate probe placement was confirmed in all subjects with magnetic resonance imag ing, Results: Collectively, the results support the feasibility of a repeat ed-measures design. Stability of tissue integrity after repeated probe inse rtion was supported by measurement of consistent basal levels of dopamine a nd its metabolites across several experiments, observation of potassium-ind uced dopamine release and absence of significant glial proliferation as ass essed by GFAP (glial fibrillary acidic protein) immunochemistry. Moreover, peak drug effects and time-course of action were similar when multiple prob es were positioned in the same anatomical site over several experiments. Co caine (1.0 mg/kg i.m.) and GBR 12909 (3.0 mg/kg i.m.) elevated extracellula r dopamine to approximately 300% of basal levels, but GBR 12909 produced a slower, more sustained elevation than cocaine. Conclusions: The results val idate the use of microdialysis in awake primates using repeated sampling of the same anatomical site and demonstrate orderly changes in extracellular dopamine following administration of dopamine uptake inhibitors.