title: Dopamine ups and downs in vulnerability to addictions: a neurodevelopmental model.
abstract: Addictions are commonly presaged by problems in childhood and adolescence. For many individuals this starts with the early expression of impulsive risk-taking, social gregariousness, and oppositional behaviors. Here we propose that these early diverse manifestations reflect a heightened ability of emotionally salient stimuli to activate dopamine pathways that foster behavioral approach. If substance use is initiated, these at-risk youth can also develop heightened responses to drug-paired cues. Through conditioning and drug-induced sensitization, these effects strengthen and accumulate, leading to responses that exceed those elicited by other rewards. At the same time, cues not paired with drug become associated with comparatively lower dopamine release, accentuating further the difference between drug and non-drug rewards. Together, these enhancing and inhibiting processes steer a pre-existing vulnerability toward a disproportionate concern for drugs and drug-related stimuli. Implications for prevention and treatment are discussed.
authors.affiliation: Department of Psychiatry, McGill University, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada; Department of Psychology, McGill University, Montreal, Quebec, Canada; Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Quebec, Canada. Electronic address: marco.leyton@mcgill.ca.
authors.forename: Marco
authors.initials: M
authors.lastname: Leyton
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, IL, USA; Committee on Neurobiology, The University of Chicago, Chicago, IL, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Vezina
mesh_terms: D016739:Behavior, Addictive / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D009420:Nervous System / Q000254:growth & development*; D019966:Substance-Related Disorders / Q000378:metabolism*
chemical_list: D004298:Dopamine
keywords: alcohol abuse; allostasis; conditioning; drug abuse; externalizing; incentive salience; reward; sensitization