High levels of dopamine D2 receptors in unaffected members of alcoholic families: possible protective factors.
paper
Primary
Public
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- Authors
- Volkow, Nora D; Wang, Gene-Jack; Begleiter, Henri; Porjesz, Bernice; Fowler, Joanna S; Telang, Frank; Wong, Christopher; Ma, Yeming; Logan, Jean; Goldstein, Rita; Alexoff, David; Thanos, Peter K
- Year
- 2006
- Journal
- Archives of general psychiatry
- PMID
- 16953002
- DOI
- 10.1001/archpsyc.63.9.999
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 D(2) receptors in striatum, and increasing D(2) receptor levels in laboratory animals reduces alcohol consumption. OBJECTIVES: To test whether high levels of D(2) receptors 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 D(2) receptors 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 D(2) receptors was significantly higher in caudate and ventral striatum in family-positive than family-negative subjects. In family-positive but not family-negative subjects, striatal D(2) receptors 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 D(2) receptor availability in nonalcoholic members of alcoholic families supports the hypothesis that high levels of D(2) receptors may protect against alcoholism. The significant associations between D(2) receptors and metabolism in frontal regions involved with emotional reactivity and executive control suggest that high levels of D(2) receptors could protect against alcoholism by regulating circuits involved in inhibiting behavioral responses and in controlling emotions.
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| Association of low striatal dopamine d2 receptor availability with nicotine dependence similar to that seen with other drugs of abuse. | Fehr C et al. | — | 2008 | → |
| Attention deficit hyperactivity disorder and substance use disorders. | Szobot CM et al. | — | 2008 | → |
| Behavioral disinhibition and the development of early-onset addiction: common and specific influences. | Iacono WG et al. | — | 2008 | → |
| Cocaine abuse and sensitization of striatal dopamine transmission: a critical review of the preclinical and clinical imaging literature. | Narendran R et al. | — | 2008 | → |
| Decreased volume of the brain reward system in alcoholism. | Makris N et al. | — | 2008 | → |
| Dopaminergic mutations: within-family association and linkage in multiplex alcohol dependence families. | Hill SY et al. | — | 2008 | → |
| Enhanced dopamine D2 receptor function in hypothalamus and corpus striatum: their role in liver, plasma and in vitro hepatocyte ALDH regulation in ethanol treated rats. | Akash KG et al. | — | 2008 | → |
| Frontal white matter and cingulum diffusion tensor imaging deficits in alcoholism. | Harris GJ et al. | — | 2008 | → |
| Functional connectivity of human striatum: a resting state FMRI study. | Di Martino A et al. | — | 2008 | → |
| Haplotypic variants in DRD2, ANKK1, TTC12, and NCAM1 are associated with comorbid alcohol and drug dependence. | Yang BZ et al. | — | 2008 | → |
| Inhibitory control deficits in childhood and risk for substance use disorders: a review. | Ivanov I et al. | — | 2008 | → |
| Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors. | Volkow ND et al. | — | 2008 | → |
| Overlapping neuronal circuits in addiction and obesity: evidence of systems pathology. | Volkow ND et al. | — | 2008 | → |
| Positron emission tomography as a tool for studying alcohol abuse. | Thanos PK et al. | — | 2008 | → |
| Proton magnetic resonance spectroscopy in alcohol use disorders: a potential new endophenotype? | Meyerhoff DJ et al. | — | 2008 | → |
| Repeated social defeat stress-induced sensitization to the locomotor activating effects of d-amphetamine: role of individual differences. | Dietz DM et al. | — | 2008 | → |
| Striatal dopamine D2 receptor binding and dopamine release during cue-elicited craving in recently abstinent opiate-dependent males. | Zijlstra F et al. | — | 2008 | → |
| Decreased dopamine D(2) receptor function in cerebral cortex and brain stem: their role in hepatic ALDH regulation in ethanol treated rats. | George AK et al. | — | 2007 | → |
| Dopamine genes and reward dependence in adolescents with excessive internet video game play. | Han DH et al. | — | 2007 | → |
| Gene \Narcotic Attenuation Program attenuates substance use disorder, a clinical subtype of reward deficiency syndrome. | Chen TJ et al. | — | 2007 | → |
| Imaging the neurochemistry of alcohol and substance abuse. | Martinez D et al. | — | 2007 | → |
| Profound decreases in dopamine release in striatum in detoxified alcoholics: possible orbitofrontal involvement. | Volkow ND et al. | — | 2007 | → |
| Transient overexpression of striatal D2 receptors impairs operant motivation and interval timing. | Drew MR et al. | — | 2007 | → |