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Neuropsychopharmacology. 2014 Sep;39(10):2441-9. doi: 10.1038/npp.2014.96. Epub 2014 May 7.

Phasic mesolimbic dopamine signaling encodes the facilitation of incentive motivation produced by repeated cocaine exposure.

Author information

1
1] Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Los Angeles, CA, USA [2] Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA [3] Department of Anesthesiology and Perioperative Care, University of California at Irvine, Irvine, CA, USA.
2
NIDDK, National Institutes of Health, Bethesda, MD, USA.
3
1] Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA [2] Department of Psychology, University of California at Los Angeles, Los Angeles, CA, USA.
4
1] Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Los Angeles, CA, USA [2] Brain Research Institute, University of California at Los Angeles, Los Angeles, CA, USA.

Abstract

Drug addiction is marked by pathological drug seeking and intense drug craving, particularly in response to drug-related stimuli. Repeated psychostimulant administration is known to induce long-term alterations in mesolimbic dopamine (DA) signaling that are hypothesized to mediate this heightened sensitivity to environmental stimuli. However, there is little direct evidence that drug-induced alteration in mesolimbic DA function underlies this hypersensitivity to motivational cues. In the current study, we tested this hypothesis using fast-scan cyclic voltammetry to monitor phasic DA signaling in the nucleus accumbens core of cocaine-pretreated (6 once-daily injections of 15 mg/kg, i.p.) and drug-naive rats during a test of cue-evoked incentive motivation for food-the Pavlovian-to-instrumental transfer task. We found that prior cocaine exposure augmented both reward seeking and DA release triggered by the presentation of a reward-paired cue. Furthermore, cue-evoked DA signaling positively correlated with cue-evoked food seeking and was found to be a statistical mediator of this behavioral effect of cocaine. Taken together, these findings provide support for the hypothesis that repeated cocaine exposure enhances cue-evoked incentive motivation through augmented phasic mesolimbic DA signaling. This work sheds new light on a fundamental neurobiological mechanism underlying motivated behavior and its role in the expression of compulsive reward seeking.

PMID:
24804846
PMCID:
PMC4138756
DOI:
10.1038/npp.2014.96
[Indexed for MEDLINE]
Free PMC Article
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