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Title: Addiction: Beyond dopamine reward circuitry

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 disruptionmore » 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.« less

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE SC OFFICE OF SCIENCE (SC)
OSTI Identifier:
1040536
Report Number(s):
BNL-96460-2011-JA
Journal ID: ISSN 0027-8424; PNASA6; R&D Project: MO-085; KP1602010; TRN: US1202489
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 108; Journal Issue: 37; Journal ID: ISSN 0027-8424
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BRAIN; DOPAMINE; DRUG ABUSE; POSITRON COMPUTED TOMOGRAPHY; prefrontal cortex; dorsal striatum; substance use disorders; stimulant drugs; brain imaging; positron emission tomography (PET)

Citation Formats

Volkow, N D, Wang, G, Volkow, N D, Wang, G -J, Fowler, J S, Tomasi, D, and Telang, F. Addiction: Beyond dopamine reward circuitry. United States: N. p., 2011. Web. doi:10.1073/pnas.1010654108.
Volkow, N D, Wang, G, Volkow, N D, Wang, G -J, Fowler, J S, Tomasi, D, & Telang, F. Addiction: Beyond dopamine reward circuitry. United States. https://doi.org/10.1073/pnas.1010654108
Volkow, N D, Wang, G, Volkow, N D, Wang, G -J, Fowler, J S, Tomasi, D, and Telang, F. 2011. "Addiction: Beyond dopamine reward circuitry". United States. https://doi.org/10.1073/pnas.1010654108.
@article{osti_1040536,
title = {Addiction: Beyond dopamine reward circuitry},
author = {Volkow, N D and Wang, G and Volkow, N D and Wang, G -J and Fowler, J S and Tomasi, D and Telang, F},
abstractNote = {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.},
doi = {10.1073/pnas.1010654108},
url = {https://www.osti.gov/biblio/1040536}, journal = {Proceedings of the National Academy of Sciences of the United States of America},
issn = {0027-8424},
number = 37,
volume = 108,
place = {United States},
year = {Tue Sep 13 00:00:00 EDT 2011},
month = {Tue Sep 13 00:00:00 EDT 2011}
}