Increased impulsivity during withdrawal from cocaine self-administration: Role for ΔFosB in the orbitofrontal cortex

Catharine A. Winstanley, Ryan K. Bachtell, David E H Theobald, Samuel Laali, Thomas A. Green, Arvind Kumar, Sumana Chakravarty, David W. Self, Eric J. Nestler

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Increased impulsivity caused by addictive drugs is believed to contribute to the maintenance of addiction and has been linked to hypofunction within the orbitofrontal cortex (OFC). Recent data indicate that cocaine "self-administration" induces the transcription factor ΔFosB in the OFC that alters the effects of investigator-administered cocaine on impulsivity. Here, using viral-mediated gene transfer, the effects of overexpressing ΔFosB within the OFC were assessed on the cognitive sequelae of chronic cocaine self-administration as measured by the 5-choice serial reaction time task (5CSRT). Cognitive testing occurred in the mornings, and self-administration sessions in the evenings, to enable the progressive assessment of repeated volitional drug intake on performance. Animals self-administering cocaine initially made more omissions and premature or impulsive responses on the 5CSRT but quickly developed tolerance to these disruptive effects. However, withdrawal from cocaine dramatically increased premature responding. When access to cocaine was increased, animals overexpressing ΔFosB failed to regulate their intake as effectively and were more impulsive during withdrawal. In summary, rats develop tolerance to the cognitive disruption caused by cocaine self-administration and show a deficit in impulse control that is unmasked during withdrawal. Our findings suggest that induction of ΔFosB within the OFC is one mediator of these effects and, thereby, increases vulnerability to addiction.

Original languageEnglish (US)
Pages (from-to)435-444
Number of pages10
JournalCerebral Cortex
Volume19
Issue number2
DOIs
StatePublished - Feb 1 2009

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Keywords

  • 5-choice serial reaction time task
  • Addiction
  • Relapse
  • Transcription factors
  • Withdrawal

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Winstanley, C. A., Bachtell, R. K., Theobald, D. E. H., Laali, S., Green, T. A., Kumar, A., Chakravarty, S., Self, D. W., & Nestler, E. J. (2009). Increased impulsivity during withdrawal from cocaine self-administration: Role for ΔFosB in the orbitofrontal cortex. Cerebral Cortex, 19(2), 435-444. https://doi.org/10.1093/cercor/bhn094