Withdrawal from cocaine self-administration produces long-lasting deficits in orbitofrontal-dependent reversal learning in rats.
Drug addicts make poor decisions. These decision-making deficits have been modeled in addicts and laboratory animals using reversal-learning tasks. However, persistent reversal-learning impairments have been shown in rats and monkeys only after noncontingent cocaine injections. Current thinking holds that to represent the human condition effectively, animal models of addiction must utilize self-administration procedures in which drug is earned contingently; thus, it remains unclear whether reversal-learning deficits caused by noncontingent cocaine exposure are relevant to addiction. To test whether reversal learning deficits are caused by contingent cocaine exposure, we trained rats to self-administer cocaine, assessed cue-induced cocaine seeking in extinction tests after 1 and 30 d of withdrawal, and then tested for reversal learning more than a month later. We found robust time-dependent increases in cue-induced cocaine seeking in the two extinction tests (incubation of craving) and severe reversal-learning impairments.
Calu
Donna J
DJ
Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Stalnaker
Thomas A
TA
Franz
Theresa M
TM
Singh
Teghpal
T
Shaham
Yavin
Y
Schoenbaum
Geoffrey
G
D000818:Animals; D016739:Behavior, Addictive; D003042:Cocaine / Q000008:administration & dosage* / Q000009:adverse effects*; D003463:Cues; D005108:Extinction, Psychological; D005625:Frontal Lobe / Q000503:physiopathology*; D007859:Learning Disabilities / Q000209:etiology* / Q000503:physiopathology*; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D012193:Reversal Learning; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000150:complications* / Q000523:psychology; D013997:Time Factors
D003042:Cocaine