Pw. Czoty et al., Cocaine-induced changes in extracellular dopamine determined by microdialysis in awake squirrel monkeys, PSYCHOPHAR, 148(3), 2000, pp. 299-306
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.