Cortical activation during cocaine use and extinction in rhesus monkeys

            Acute re-exposure to cocaine or drug cues associated with cocaine use can elicit drug cravings and relapse. Acute cocaine administration increased cerebral blood flow mainly in the frontal and parietal regions. FMRI studies have shown patterns of brain activation following cocaine administration. Regions including cingulated and lateral prefrontal cortex showed short duration activations that were correlated with ratings of “rush”. Nucleus accumbens showed sustained activation associated with ratings of “craving”.

            This study was the first one to use nonhuman primates in measuring acute cocaine use changes in brain activity. First, cocaine was administered noncontingently. Secondly, the same subjects were trained to self administer cocaine under a fixed ratio. Thirdly, the nonhuman primates were taught to self administer cocaine under a complex , second order schedule.

            Drug administration was not contingent on a behavioral response by the subjects. Cocaine induced a significant increase in whole brain blood flow. Self administration behavior remained robust even in the absence of cocaine delivery. All subjects also learned to self administer under the complex, two step delivery system.

            The areas of major activation included the anterior cingulated cortex, a region associated with the extended limbic system. Self administered cocaine led to greater increases in extracellular dopamine in the nucleus accumbens.

Psychopharmacology (2010) 208: 191-199
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