title: Adolescent Alcohol Exposure Amplifies the Incentive Value of Reward-Predictive Cues Through Potentiation of Phasic Dopamine Signaling.
abstract: Adolescent alcohol use remains a major public health concern due in part to well-established findings implicating the age of onset in alcohol use in the development of alcohol use disorders and persistent decision-making deficits in adults. We have previously demonstrated that moderate adolescent alcohol consumption in rats promotes suboptimal decision making and an associated perturbation in mesolimbic dopamine transmission in adulthood. Dopamine-dependent incentive learning processes are an integral component of value-based decision making and a fundamental element to many theoretical accounts of addiction. Thus we tested the hypothesis that adolescent alcohol use selectively alters incentive learning processes through perturbation of mesolimbic dopamine systems. To assess incentive learning, behavioral and neurochemical measurements were made during the acquisition, maintenance, extinction, and reacquisition of a Pavlovian conditioned approach procedure in adult rats with a history of adolescent alcohol consumption. We show that moderate adolescent alcohol consumption potentiates stimulus-evoked phasic dopamine transmission, measured in vivo by fast-scan cyclic voltammetry, in adulthood and biases individuals toward a dopamine-dependent incentive learning strategy. Moreover, we demonstrate that animals exposed to alcohol in adolescence are more sensitive to an unexpected variation in reward outcomes. This pattern of phasic dopamine signaling and the associated bias in learning may provide a mechanism for the well-documented vulnerability of individuals with early-life alcohol use for alcohol use disorders in adulthood.
authors.affiliation: Department of Animals in Science and Society, Division of Behavioral Neuroscience, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Marcia
authors.initials: M
authors.lastname: Spoelder
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA.
authors.forename: Kimberly T
authors.initials: KT
authors.lastname: Tsutsui
authors.affiliation: Department of Animals in Science and Society, Division of Behavioral Neuroscience, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Heidi M B
authors.initials: HM
authors.lastname: Lesscher
authors.affiliation: Department of Animals in Science and Society, Division of Behavioral Neuroscience, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.|Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Louk J M J
authors.initials: LJ
authors.lastname: Vanderschuren
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Clark
mesh_terms: D000818:Animals; D059031:Anticipation, Psychological / Q000187:drug effects / Q000502:physiology; D002492:Central Nervous System Depressants / Q000633:toxicity*; D003214:Conditioning, Classical / Q000187:drug effects* / Q000502:physiology; D003463:Cues; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004567:Electrodes, Implanted; D000431:Ethanol / Q000633:toxicity*; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D017207:Rats, Sprague-Dawley; D012201:Reward; D000066608:Underage Drinking
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D004298:Dopamine