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Effects of Chronic Cocaine Self-Administration on Cognition and Cerebral Glucose Utilization in Rhesus Monkeys

  • Robert W. Gould
    Affiliations
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina
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  • H. Donald Gage
    Affiliations
    Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina
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  • Michael A. Nader
    Correspondence
    Address correspondence to Michael A. Nader, Ph.D., Wake Forest University School of Medicine, Department of Physiology and Pharmacology, Medical Center Boulevard, 546 NRC, Winston-Salem, NC 27157-1083
    Affiliations
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina

    Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina
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      Background

      Chronic cocaine use is associated with neurobiological and cognitive deficits that persist into abstinence, hindering success of behavioral treatment strategies and perhaps increasing likelihood of relapse. The effects of current cocaine use and abstinence on neurobiology and cognition are not well characterized.

      Methods

      Adult male rhesus monkeys with an extensive cocaine self-administration history (∼ 5 years) and age-matched control animals (n = 4/group) performed cognitive tasks in morning sessions and self-administered cocaine or food in afternoon sessions. Positron emission tomography and [18F]-fluorodeoxyglucose were employed to assess cerebral metabolic rates of glucose utilization during cognitive testing.

      Results

      Cocaine-experienced monkeys required significantly more trials and committed more errors on reversal learning and multidimensional discriminations, compared with control animals. Cocaine-naive, but not cocaine-experienced, monkeys showed greater metabolic rates of glucose utilization during a multidimensional discrimination task in the caudate nucleus, hippocampus, anterior and posterior cingulate, and regions associated with attention, error detection, memory, and reward. Using a delayed match-to-sample task, there were no differences in baseline working memory performance between groups. High-dose cocaine self-administration disrupted delayed match-to-sample performance but tolerance developed. Acute abstinence from cocaine did not affect performance, but by day 30 of abstinence, accuracy increased significantly, while performance of cocaine-naive monkeys was unchanged.

      Conclusions

      These data document direct effects of cocaine self-administration on cognition and neurobiological sequelae underlying cognitive deficits. Improvements in working memory can occur in abstinence, albeit across an extended period critical for treatment seekers, suggesting pharmacotherapies designed to enhance cognition may improve success of current behavioral modification strategies.

      Key Words

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      Linked Article

      • Cognitive Consequences of Alterations in Functional Circuitry Induced by Chronic Cocaine Use and the Potential Impact for Treatment
        Biological PsychiatryVol. 72Issue 10
        • Preview
          Chronic cocaine exposure induces changes in brain function that persist into abstinence. Although direct mechanisms of action on glutamatergic and dopaminergic transmission have been identified, there are long-term consequences for corticostriatal function and cognition. The extent to which perturbations in functional circuitry persist during abstinence may predict the efficacy of different treatments depending on distinct cognitive processes. In Gould et al. (1), the effects of chronic cocaine were examined on cognitive flexibility—the ability to switch responses away from one stimulus to another, based on learning from outcome and selective attention.
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