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Cited by 44Neurotransmitter Receptor Influence on BehaviorSubstance Abuse Treatment and OutcomesNeural and Behavioral Psychology Studies

High Levels of Dopamine D2 Receptors in Unaffected Members of Alcoholic Families: Possible Protective Factors

Volkow, Nora D., Wang, Gene-Jack, Begleiter, Henri, Porjesz, Bernice, Fowler, Joanna S., Telang, Frank, Wong, Christopher, Ma, Yeming +4 more·2006·Archives of General Psychiatry
DOI 10.1001/archpsyc.63.9.999
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Abstract

Context Predisposition to alcoholism is likely an interaction between genetic and environmental factors that confer vulnerability and protection. Alcoholic subjects have low levels of dopamine D2receptors in striatum, and increasing D2receptor levels in laboratory animals reduces alcohol consumption. Objectives To test whether high levels of D2receptors may be protective against alcoholism and whether this is mediated by their modulation of activity in orbitofrontal cortex and cingulate gyrus (regions involved in salience attribution, emotional reactivity, and inhibitory control). Design Research (nonalcoholic subjects with a family history of alcoholism) and comparison (nonalcoholic subjects with a negative family history) sample. Setting Outpatient setting. Participants Fifteen nonalcoholic subjects who had an alcoholic father and at least 2 other first- or second-degree relatives who were alcoholics (family-positive group) and 16 nonalcoholic controls with no family history of alcoholism (family-negative group). Main Outcome Measures Results of positron emission tomography with raclopride C 11 to assess D2receptors and with fludeoxyglucose F 18 to assess brain glucose metabolism (marker of brain function). Personality measures were obtained with the Multidimensional Personality Questionnaire. Results Availability of D2receptors was significantly higher in caudate and ventral striatum in family-positive than family-negative subjects. In family-positive but not family-negative subjects, striatal D2receptors were associated with metabolism in anterior cingulate (Brodmann area 24/25) and orbitofrontal (Brodmann area 11) and prefrontal (Brodmann area 9/10) cortices, and with personality scores of positive emotionality. Conclusions The higher-than-normal D2receptor availability in nonalcoholic members of alcoholic families supports the hypothesis that high levels of D2receptors may protect against alcoholism. The significant associations between D2receptors and metabolism in frontal regions involved with emotional reactivity and executive control suggest that high levels of D2receptors could protect against alcoholism by regulating circuits involved in inhibiting behavioral responses and in controlling emotions.

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  • In individuals at high genetic risk for alcohol use disorder who do not themselves suffer from alcohol use disorder, striatal D2 receptor upregulation may be protective by strengthening prefrontal circuits involved in self-regulation.

    “In these high- risk indi viduals, the striatal D2 receptor upregulation may be protective against alcohol use disorder by strengthening prefrontal circuits involved in self- regulation 61 .”

    From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [61]

  • In subjects at high risk for alcoholism who were not alcoholics, higher than normal striatal D2R availability was associated with normal metabolism in OFC, ACC, and DLPFC.

    “a study performed in subjects who, despite having a high risk for alcoholism (positive family history of alcoholism) were not alcoholics, revealed a higher than normal striatal D2R availability that was associated with normal metabolism in OFC, ACC and DLPFC (77).”

    From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [77]

  • Subjects with high genetic risk for alcoholism who were not alcoholic had higher than normal striatal D2R associated with normal prefrontal metabolism, which might have protected them.

    “Indeed, we showed that subjects who, despite having a high genetic risk for alcoholism (positive family history of alcoholism) were not alcoholics, had higher than normal striatal D2R, which was associated with normal prefrontal metabolism (81) that might have protected them from alcoholism.”

    From The Addictive Dimensionality of Obesity (2013) · cites this paper as [81]

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Authors
Volkow, N. D., Wang, G.-J., Begleiter, H., Porjesz, B., Fowler, J. S., Telang, F., Wong, C., Ma, Y., Logan, J., Goldstein, R., Alexoff, D., & Thanos, P. K.
Affiliations
National Institute on Drug Abuse (US)
ORCID
Venue
Archives of General Psychiatry
Publisher
American Medical Association (AMA)
Published
2006-09-01
Volume
63
Issue
9
Pages
999
ISSN
0003-990X (ISSN-L)
DOI
10.1001/archpsyc.63.9.999
OpenAlex
W2105393014
Cited by
2
References
58
Citations by year
2019: 1
FWCI
0.00
Type
journal article
Language
en
Open access
closed
Locations
Archives of General Psychiatry (publishedVersion)
Funders
National Institute on Alcohol Abuse and Alcoholism (AA-09481)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords
dopamine D2 receptor, alcoholism, family history of alcoholism, genetic susceptibility, striatum, caudate nucleus, ventral striatum, brain glucose metabolism, orbitofrontal cortex, anterior cingulate cortex, prefrontal cortex, positive affectivity, personality, emotional reactivity, executive function, raclopride

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