Effects of cocaine rewards on neural representations of cognitive demand in nonhuman primates

Rationale: Investigations of the neural consequences of the effects of cocaine on cognition have centered on specific brain circuits including prefrontal cortex, medial temporal lobe and striatum and their roles in controlling drug dependent behavior and addiction. These regions are critical to many aspects of drug abuse; however recent investigations in addicted individuals have reported possible cognitive deficits that impact recovery and other therapeutic interventions. Objectives: Therefore a direct assessment of the effects of cocaine as a reward for cognitive function provides a means of determining how brain systems involved such as prefrontal cortex are affected under normal vs. conditions of acute drug exposure as a precursor to the final impaired function in the addicted state. Methods: Nonhuman primates (NHPs) were tested in a delayed-match-to-sample decision making task to determine effects of high vs. low cognitive load trials on single neuron activity and fluorodeoxyglucose-positron emission tomography (FDG-PET) determined metabolic activation of prefrontal cortex when juice vs. intravenous cocaine were employed as rewards for successful performance. Results: Cognitive processing in prefrontal cortex was altered primarily on high load trials in which cocaine was randomly presented as the signaled and delivered reward on particular trials. The detrimental actions of cocaine rewards were also shown to persist and impair task performance on subsequent juice rewarded trials. Conclusions: The findings indicate that one of the ways in which cocaine use may disrupt performance of a cognitive task is to alter neural processing in prefrontal cortex when involved in discriminating circumstances on the basis of low vs. high cognitive demand.