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

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Appetitive Behavior / drug effects
  • Appetitive Behavior / physiology
  • Cocaine / administration & dosage
  • Cocaine-Related Disorders / physiopathology*
  • Conditioning, Classical / drug effects
  • Conditioning, Classical / physiology
  • Cues
  • Dopamine / metabolism*
  • Dopamine Uptake Inhibitors / administration & dosage
  • Drug-Seeking Behavior / physiology*
  • Food
  • Linear Models
  • Male
  • Motivation / drug effects*
  • Motivation / physiology
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / physiopathology
  • Periodicity
  • Rats, Sprague-Dawley
  • Transfer, Psychology / drug effects
  • Transfer, Psychology / physiology


  • Dopamine Uptake Inhibitors
  • Cocaine
  • Dopamine