Altered cerebellar and prefrontal cortex function in rhesus monkeys that previously self-administered cocaine.

RATIONALE

Differences in brain function in cocaine users can occur even when frank deficits are not apparent, indicating neuroadaptive consequences of use. Using monkeys to investigate altered metabolic activity following chronic cocaine self-administration allows an assessment of altered function due to cocaine use, without confounding pre-existing differences or polysubstance use often present in clinical studies.

OBJECTIVES

To evaluate alterations in metabolic function during a working memory task in the prefrontal cortex and the cerebellum following 1 year of chronic cocaine self-administration followed by a 20 month drug-free period.

METHODS

Fluorodeoxyglucose ((18)F) PET imaging was used to evaluate changes in relative regional metabolic activity associated with a delayed match to sample working memory task. Chronic cocaine animals were compared to a control group, and region of interest analyses focused on the dorsolateral prefrontal cortex (DLPFC) and cerebellum.

RESULTS

Despite no differences in task performance, in the cocaine group, the cerebellum showed greater metabolic activity during the working memory task (relative to the control task) compared to the control group. There was also a trend toward a significant difference between the groups in DLPFC activity (p = 0.054), with the cocaine group exhibiting lower DLPFC metabolic activity during the delay task (relative to the control task) than the control group.

CONCLUSION

The results support clinical indications of increased cerebellar activity associated with chronic cocaine exposure. Consistent with evidence of functional interactions between cerebellum and prefrontal cortex, these changes may serve to compensate for potential impairments in functionality of DLPFC.