Evidence of Temporal Cortical Dysfunction in Rhesus Monkeys following Chronic Cocaine Self-Administration

• Published in: Cerebral cortex (New York, N.Y. 1991) Vol. 18; no. 9; pp. 2109 - 2116
• Main Authors: Liu, S., Heitz, R. P., Sampson, A. R., Zhang, W., Bradberry, C. W.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01-09-2008; Oxford Publishing Limited (England)
• Subjects: addiction; Animals; Chronic Disease; Cocaine - analogs & derivatives; Cocaine - pharmacology; Cocaine-Related Disorders - physiopathology; cognition; Cognition Disorders - chemically induced; Cognition Disorders - physiopathology; Conditioning (Psychology) - drug effects; Conditioning (Psychology) - physiology; Discrimination (Psychology) - drug effects; Discrimination (Psychology) - physiology; Dopamine Uptake Inhibitors - pharmacology; Female; Macaca mulatta; Male; prefrontal; Prefrontal Cortex - drug effects; Prefrontal Cortex - physiopathology; primate; Psychomotor Performance - drug effects; Psychomotor Performance - physiology; psychostimulant; Reversal Learning - drug effects; Reversal Learning - physiology; Self Administration; primate; cognition; prefrontal; psychostimulant; addiction
• ISSN: 1047-3211; 1460-2199
• DOI: 10.1093/cercor/bhm236

Cocaine abusers show impaired performance on cognitive tasks that engage prefrontal cortex. These deficits may contribute to impaired control and relapse in abusers. Understanding the neuronal substrates that lead to these deficits requires animal models that are relevant to the human condition. However, to date, models have mostly focused on behaviors mediated by subcortical systems. Here we evaluated the impact of long-term self-administration of cocaine in the rhesus monkey on cognitive performance. Tests included stimulus discrimination (SD)/reversal and delayed alternation tasks. The chronic cocaine animals showed marked deficits in ability to organize their behavior for maximal reward. This was demonstrated by an increased time needed to acquire SDs. Deficits were also indicated by an increased time to initially learn the delayed alternation task, and to adapt strategies for bypassing a reliance on working memory to respond accurately. Working memory per se (delay dependent performance) was not affected by chronic self-administration. This pattern of cognitive deficits suggests dysfunction that extends beyond localized prefrontal cortical areas. In particular, it appears that temporal cortical function is also compromised. This agrees with other recent clinical and preclinical findings, and suggests further study into addiction related dysfunction across more widespread cortical networks is warranted.