Addiction: Beyond dopamine reward circuitry

Nora D. Volkow, Gene Jack Wang, Joanna S. Fowler, Dardo Tomasi, Frank Telang

Research output: Contribution to journalReview articlepeer-review

653 Scopus citations

Abstract

Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction is much less clear. This review focuses on studies that used PET to characterize the brain DA system in addicted subjects. These studies have corroborated in humans the relevance of drug-induced fast DA increases in striatum [including nucleus accumbens (NAc)] in their rewarding effects but have unexpectedly shown that in addicted subjects, drug-induced DA increases (as well as their subjective reinforcing effects) are markedly blunted compared with controls. In contrast, addicted subjects show significant DA increases in striatum in response to drug-conditioned cues that are associated with self-reports of drug craving and appear to be of a greater magnitude than the DA responses to the drug. We postulate that the discrepancy between the expectation for the drug effects (conditioned responses) and the blunted pharmacological effects maintains drug taking in an attempt to achieve the expected reward. Also, whether tested during early or protracted withdrawal, addicted subjects show lower levels of D2 receptors in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (anterior cingulate gyrus), whose disruption results in compulsivity and impulsivity. These results point to an imbalance between dopaminergic circuits that underlie reward and conditioning and those that underlie executive function (emotional control and decision making), which we postulate contributes to the compulsive drug use and loss of control in addiction.

Original languageEnglish
Pages (from-to)15037-15042
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number37
DOIs
StatePublished - 13 Sep 2011
Externally publishedYes

Keywords

  • Brain imaging
  • Dorsal striatum
  • Prefrontal cortex
  • Stimulant drugs
  • Substance use disorders

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