title: Phasic mesolimbic dopamine signaling encodes the facilitation of incentive motivation produced by repeated cocaine exposure.
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.
authors.affiliation: 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.
authors.forename: Sean B
authors.initials: SB
authors.lastname: Ostlund
authors.affiliation: NIDDK, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Kimberly H
authors.initials: KH
authors.lastname: LeBlanc
authors.affiliation: 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.
authors.forename: Alisa R
authors.initials: AR
authors.lastname: Kosheleff
authors.affiliation: 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.
authors.forename: Kate M
authors.initials: KM
authors.lastname: Wassum
authors.affiliation: 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.
authors.forename: Nigel T
authors.initials: NT
authors.lastname: Maidment
mesh_terms: D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D003463:Cues; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D058999:Drug-Seeking Behavior / Q000502:physiology*; D005502:Food; D016014:Linear Models; D008297:Male; D009042:Motivation / Q000187:drug effects* / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000503:physiopathology; D010507:Periodicity; D017207:Rats, Sprague-Dawley; D014163:Transfer, Psychology / Q000187:drug effects / Q000502:physiology
chemical_list: D018765:Dopamine Uptake Inhibitors; D003042:Cocaine; D004298:Dopamine