The D<sub>2</sub> Dopamine Receptor Gene as a Determinant of Reward Deficiency Syndrome

Blum, Kenneth; Sheridan, Peter J.; Wood, Robert C.; Braverman, Eric R.; Chen, T J H; Cull, John G.; Comings, David E.

doi:10.1177/014107689608900711

Cited by 404 publications

(308 citation statements)

References 51 publications

(2 reference statements)

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“…In addition, research on vulnerability to pathological gambling has emphasized the importance of the D2 receptor in genetic risk for this disorder (Comings et al, 1996). This is in line with other research indicating a strong link between anomalies in genes that code for the D2 receptor and risk for a variety of addictive-compulsive disorders (Blum et al, 1995(Blum et al, , 1996.…”

Section: Introductionsupporting

confidence: 76%

A D2 Antagonist Enhances the Rewarding and Priming Effects of a Gambling Episode in Pathological Gamblers

Zack

Poulos

2007

Neuropsychopharmacol

152

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Previous research indicated shared neurochemical substrates for gambling and psychostimulant reward. This suggests that dopamine substrates may directly govern the reinforcement process in pathological gambling. To investigate this issue, the present study assessed the effects of the relatively selective dopamine D2 antagonist, haloperidol (3 mg, oral) on responses to actual gambling (15 min on a slot machine) in 20 non-comorbid pathological gamblers and 18 non-gambler controls in a placebo-controlled, double-blind, counterbalanced design. In gamblers, haloperidol significantly increased self-reported rewarding effects of gambling, post-game priming of desire to gamble, facilitation of reading speed to Gambling words, and gambling-induced elevation in blood pressure. In controls, haloperidol augmented gambling-induced elevation in blood pressure, but had no effect on other indices. The findings provide direct experimental evidence that the D2 substrate modulates gambling reinforcement in pathological gamblers.

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Section: Introductionsupporting

confidence: 76%

A D2 Antagonist Enhances the Rewarding and Priming Effects of a Gambling Episode in Pathological Gamblers

Zack

Poulos

2007

Neuropsychopharmacol

152

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“…Structural malfunction in this system may increase risk for drug-seeking behaviors and Reward Deficiency Syndrome (1,89). These abnormalities may reflect a genetically influenced alteration in alcoholism (90).…”

Section: Frontolimbic Relationships Within the Reward-networkmentioning

confidence: 99%

Decreased Volume of the Brain Reward System in Alcoholism

Makris

Oscar‐Berman

Jaffin

et al. 2008

Biological Psychiatry

339

322

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Background-Reinforcement of behavioral responses involves a complex cerebral circuit engaging specific neuronal networks that are modulated by cortical oversight systems affiliated with emotion, memory, judgment, and decision making (collectively referred to in this study as the "extended reward and oversight system" or "reward-network"). We examined whether rewardnetwork brain volumes are reduced in alcoholics, and how volumes of subcomponents within this system are correlated with memory and drinking-history.

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“…The dopaminergic pathway mediates responsiveness to reward and is implicated in the rewarding action of abused drugs such as cocaine and alcohol. 2,3 Further evidence for the importance of the dopaminergic pathway to ADHD comes from a knockout-gene study in mice. 4 In this study, mice that were homozygous for deactivation of the dopamine transporter gene (DAT1) were five to six times more active and had dopamine remain active in the synaptic cleft 100 times longer than heterozygous and wild-type mice.…”

mentioning

confidence: 99%

The DRD2 TaqI polymorphism and symptoms of attention deficit hyperactivity disorder

et al. 1999

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Keywords: DRD2; dopamine receptor 2; attention deficit hyperactivity disorder (ADHD)The relationship of the DRD2 TaqI-A1 allele to hyperactive/impulsive and inattentive symptoms of attention deficit hyperactivity disorder (ADHD) in children and adolescents was examined in a sample of clinic-referred children and their siblings, and control children and their siblings (n = 236). The contribution of genetic dominance and additivity to mean differences among the A2A2, A1A2, and A1A1 genotypes was estimated using structural equation modeling. The effect of genetic additivity was statistically significant for both traits in an analysis of all children. The heritability from the DRD2 locus was estimated at 4.27% for hyperactiveimpulsive symptoms and 2.12% for inattentive symptoms. Children with the A2A2 genotype had the highest mean level of symptoms. To control for any possible effects of population stratification, this analysis was repeated with parental genotypes as controls. In this smaller sample, although the direction of the effect was the same as that in the whole sample, the genotypic differences failed to reach conventional significance levels and the effect sizes were smaller (h 2 = 1.62% and 0.79%, respectively). Furthermore, a genotype relative risk test of children who had questionnaire-based diagnoses of ADHD also failed to yield evidence of either association or linkage. Given that the A1 allele was expected to be the high risk allele, and that results were non-significant in tests that controlled for population heterogeneity, we doubt that this DRD2 polymorphism influences symptoms of ADHD in childhood.The dopamine receptor 2 gene (DRD2) has been the focus of considerable research linking genetic polymorphisms with behavioral traits. The most frequently studied mutation in DRD2 is a TaqI restriction site in the 3Ј untranslated region of the gene. 1 It does not alter the amino acid sequence of the DRD2 protein, and its functional significance, if any, is unknown. This study examines the relation of the TaqI polymorphism to symptoms of hyperactivity-impulsivity and inattention, the symptom dimensions that underlie DSM-IV diagnoses of attention deficit hyperactivity disorder (ADHD).There is reason to expect genes in dopaminergic brain pathways to be related to childhood ADHD. The dopaminergic pathway mediates responsiveness to reward and is implicated in the rewarding action of abused drugs such as cocaine and alcohol. 2,3 Further evidence for the importance of the dopaminergic pathway to ADHD comes from a knockout-gene study in mice. 4 In this study, mice that were homozygous for deactivation of the dopamine transporter gene (DAT1) were five to six times more active and had dopamine remain active in the synaptic cleft 100 times longer than heterozygous and wild-type mice. In our previous work, we found association and linkage between ADHD and a polymorphism in DAT1 and association between ADHD and another polymorphism in the dopamine receptor D4 gene (DRD4). 5,6 There was also some evidence for heteroge...

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The D₂ Dopamine Receptor Gene as a Determinant of Reward Deficiency Syndrome

Cited by 404 publications

References 51 publications

A D2 Antagonist Enhances the Rewarding and Priming Effects of a Gambling Episode in Pathological Gamblers

A D2 Antagonist Enhances the Rewarding and Priming Effects of a Gambling Episode in Pathological Gamblers

Decreased Volume of the Brain Reward System in Alcoholism

The DRD2 TaqI polymorphism and symptoms of attention deficit hyperactivity disorder

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The D2 Dopamine Receptor Gene as a Determinant of Reward Deficiency Syndrome

Cited by 404 publications

References 51 publications

A D2 Antagonist Enhances the Rewarding and Priming Effects of a Gambling Episode in Pathological Gamblers

A D2 Antagonist Enhances the Rewarding and Priming Effects of a Gambling Episode in Pathological Gamblers

Decreased Volume of the Brain Reward System in Alcoholism

The DRD2 TaqI polymorphism and symptoms of attention deficit hyperactivity disorder

Contact Info

Product

Resources

About

The D₂ Dopamine Receptor Gene as a Determinant of Reward Deficiency Syndrome