Evidence of temporal cortical dysfunction in rhesus monkeys following chronic cocaine self-administration.
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.
Liu
S
S
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Heitz
R P
RP
Sampson
A R
AR
Zhang
W
W
Bradberry
C W
CW
D000818:Animals; D002908:Chronic Disease; D003042:Cocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000503:physiopathology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004192:Discrimination, Psychological / Q000187:drug effects / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005260:Female; D008253:Macaca mulatta; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D012193:Reversal Learning / Q000187:drug effects / Q000502:physiology; D012646:Self Administration
D018765:Dopamine Uptake Inhibitors; C066444:cocaethylene; D003042:Cocaine