Effects of chronic cocaine self-administration on cognition and cerebral glucose utilization in Rhesus monkeys.
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 [(18)F]-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.
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1083, USA.
Robert W
RW
Gould
H Donald
HD
Gage
Michael A
MA
Nader
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage / Q000009:adverse effects; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000523:psychology; D003071:Cognition / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods; D012193:Reversal Learning / Q000187:drug effects*; D012646:Self Administration; D013647:Task Performance and Analysis
D019788:Fluorodeoxyglucose F18; D003042:Cocaine; D005947:Glucose