Abnormal associative encoding in orbitofrontal neurons in cocaine-experienced rats during decision-making.

Full Abstract

Recent evidence has linked exposure to addictive drugs to an inability to employ information about adverse consequences, or outcomes, to control behavior. For instance, addicts and drug-experienced animals fail to adapt their behavior to avoid adverse outcomes in gambling and reversal tasks or after changes in the value of expected rewards. These deficits are similar to those caused by damage to the orbitofrontal cortex, suggesting that addictive drugs may cause long-lasting changes in the representation of outcome associations in a circuit that includes the orbitofrontal cortex. Here we test this hypothesis by recording from orbitofrontal neurons in a discrimination task in rats previously exposed to cocaine (30 mg/kg i.p. for 14 days). We found that orbitofrontal neurons recorded in cocaine-experienced rats failed to signal the adverse outcome at the time a decision was made in the task. The loss of this signal was associated with abnormal changes in response latencies on aversive trials. Furthermore, upon reversal of the cue-outcome associations, orbitofrontal neurons in cocaine-treated rats with enduring reversal impairments failed to reverse their cue-selectivity, while orbitofrontal neurons in cocaine-treated rats with normal performance showed an increase in the plasticity of cue-selective firing after reversal. These results provide direct neurophysiological evidence that exposure to cocaine can cause behaviorally relevant changes in the processing of associative information in a circuit that includes the orbitofrontal cortex.

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Author information

Author/s: Stalnaker, Thomas A (TA); Roesch, Matthew R (MR); Franz, Theresa M (TM); Burke, Kathryn A (KA); Schoenbaum, Geoffrey (G);

Affiliation: Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn St, HSF-2 S251, Baltimore, MD 21201, USA. tstal002(-atsign-)umaryland.edu

Grants: R01 DA015718-03 (Agency:NIDA NIH HHS) ; R01-DA015718 (Agency:NIDA NIH HHS) ; T32-DC00054 (Agency:NIDCD NIH HHS) ; T32-NS07375 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: The European journal of neuroscience (Eur J Neurosci), published in France. (Language: eng)

Reference: 2006-Nov; vol 24 (issue 9) : pp 2643-53

Dates: Created 2006/11/14; Completed 2007/01/19; Revised 2008/11/20;

PMID: 17100852, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Association Learning - drug effects
Behavior, Animal - drug effects
Cocaine - pharmacology
Decision Making - drug effects
Discrimination Learning - drug effects
Dopamine Uptake Inhibitors - pharmacology

Dopamine Uptake Inhibitors - pharmacology
Frontal Lobe - drug effects
Male
Neuronal Plasticity - drug effects
Neurons - drug effects
Rats
Rats, Long-Evans

Associated Chemicals: Dopamine Uptake Inhibitors (0) ; Cocaine (50-36-2)

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