COCAINE ALTERS CEREBRAL METABOLISM WITHIN THE VENTRAL STRIATUM AND LIMBIC CORTEX OF MONKEYS

The functional consequences of acute cocaine administration in nonhuma n primates were assessed using the quantitative 2-[C-14]deoxyglucose m ethod. Local rates of cerebral metabolism were determined after an int ravenous infusion of 1.0 mg/kg cocaine or vehicle in six awake cynomol gus monkeys (Macaca fascicularis) trained to sit calmly in a primate c hair. Cocaine administration decreased glucose utilization in a discre te set of structures that included both cortical and subcortical porti ons of the limbic system. Glucose metabolism in the core and shell of the nucleus accumbens was decreased markedly, and smaller decrements w ere observed in the caudate and anterior putamen. In addition, cocaine administration produced significant decreases in limbic cortex. Metab olism was decreased in orbitofrontal cortex (areas 11, 12o, 13, 13a, 1 3b), portions of the gyrus rectus including area 25, entorhinal cortex , and parts of the hippocampal formation. The cortical regions in whic h functional activity was altered provide dense projections to the nuc leus accumbens, and the decreased activity in these projections may be responsible in part for the large alterations in functional activity within the ventral striatum, Decreased metabolism also was evident in the anterior nuclear group of the thalamus, raphe nuclei, and locus ce ruleus, The acute cerebral metabolic effects of cocaine in the conscio us macaque, therefore, were contained primarily within a set of interc onnected limbic regions, including ventral prefrontal cortex, medial t emporal regions, the ventral striatal complex, and anterior thalamus. The decreased rates of glucose metabolism reported here resemble decre ments found using positron emission tomography in humans. In the rat, by contrast, metabolic activity increased and changes were focused in subcortical regions, The present results represent an important expans ion of the neural circuitry on which cocaine acts in the monkey as com pared with the rat, and this in turn implies that cocaine affects a br oader spectra of behaviors in primates than in rodents.