Send to

Choose Destination
See comment in PubMed Commons below
Trends Pharmacol Sci. 2014 Jun;35(6):268-76. doi: 10.1016/ Epub 2014 Apr 30.

Dopamine ups and downs in vulnerability to addictions: a neurodevelopmental model.

Author information

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:
Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, IL, USA; Committee on Neurobiology, The University of Chicago, Chicago, IL, USA.


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.


alcohol abuse; allostasis; conditioning; drug abuse; externalizing; incentive salience; reward; sensitization

[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center