Withdrawal from cocaine self-administration produces long-lasting deficits in orbitofrontal-dependent reversal learning in rats

  1. Donna J. Calu1,
  2. Thomas A. Stalnaker2,
  3. Theresa M. Franz2,
  4. Teghpal Singh1,
  5. Yavin Shaham4, and
  6. Geoffrey Schoenbaum2,3,5
  1. 1 Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA;
  2. 2 Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA;
  3. 3 Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA;
  4. 4 Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224, USA

Abstract

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.

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