A study of the dopamine D2 receptor gene in pathological gambling

Comings, David E.; Rosenthal, Richard J.; Lesieur, Henry R.; Rugle, Loreen; Muhleman, Donn; Chiu, Connie; Dietz, George; Gade, Radhika

doi:10.1097/00008571-199606000-00004

Cited by 287 publications

(156 citation 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: 75%

“…As noted in the Introduction, genetic studies have provided correlational evidence indicating that low D2 receptor function is a key risk factor for development of pathological gambling (Comings et al, 1996). Subsequent fMRI research with healthy volunteers found that those with the genetic variant (A1 allele) linked with low D2 receptor function displayed increased activation to anticipated rewards in reward-relevant brain regions during a simulated gambling task (Cohen et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

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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: 75%

Section: Discussionmentioning

confidence: 99%

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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“…It is noted that the simultaneous approach of scores, grouping the probands into four distinct base rates according to the following divisions: (1) scores all three dopaminergic genes is based on the concept of polygenic inheritance and this method was successbelow 60; (2) equal to 60 up to 73; (3) equal to 74 up to 83; and (4) equal to 84 up to 100. The demographics fully utilized most recently by Comings et al 47 to assess allelic prevalence in Tourette's disorder and a number of the subject population are described in Taq I restriction endonuclease, electrophoresis in agafor DRD 2 A 1 and A 2 alleles. Additional controls came rose, Southern transfer to a nylon filter, hybridization from three sources of volunteers attending the City of with 32 P-labeled probe, and autoradiography, demonHope Medical Center: A) adopting, foster or stepstrated fragments of 2.8 kb (B 1 ) and 1.4 kb (B 2 ).…”

Section: Introductionmentioning

confidence: 99%

Association of polymorphisms of dopamine D2 receptor (DRD2), and dopamine transporter (DAT1) genes with schizoid/avoidant behaviors (SAB)

et al. 1997

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The dopaminergic system, and in particular the dopamine D 2 receptor, has been implicated in reward mechanisms in the brain. Dysfunction of the D 2 dopamine receptors leads to aberrant substance-seeking behaviors (ethanol, drugs, tobacco, and food) and other related behaviors (pathological gambling, Tourette's disorder, attention-deficit/hyperactivity disorder). This is the first study supporting a strong association between the dopamine D 2 receptor Taq A 1 allele with schizoid/avoidant behavior (SAB). Additionally, an albeit weaker association between the 480-bp VNTR 10/10 allele of the dopamine transporter (DAT 1 ) gene with SAB was similarly found.

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“…We have observed a significant decrease in DRD3 MscI 12 heterozygosity in Tourette syndrome 10 and pathological gambling. 11 The studies of Jö nsson et al 12 showed that the mean HVA level for the 11 + 22 DRD3 homozygotes was 190 nmol L −1 compared to 161 nmol L −1 for the 12 heterozygotes (P = 0.08). Recently Krebs et al 13 reported a significant decrease in DRD3 BalI heterozygosity in 36 schizophrenics with comorbid substance abuse (30.6%) compared to 52 controls (51.9%).…”

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confidence: 97%

Homozygosity at the dopamine DRD3 receptor gene in cocaine dependence

Comings

González

et al. 1999

Mol Psychiatry

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We examined the hypothesis that the dopamine D 3 receptor gene (DRD3) is a susceptibility factor for cocaine dependence. The MscI /Bal I polymorphism of the DRD3 gene was examined in 47 Caucasian subjects with cocaine dependence and 305 Caucasian controls. Based on prior studies with a range of psychiatric disorders we hypothesized there would be a decrease in the frequency of the 12 genotype in the patient sample (increased homozygosity). We observed a significant decrease in the frequency of 12 heterozygotes in subjects with cocaine dependence (29.8%) vs controls (46.9%) (P Յ 0.028). This percentage was still lower in those who had chronically used cocaine for more than 10 years (25%), or more than 15 years (21.5%). The DRD3 gene accounted for 1.64% of the variance of cocaine dependence. The DRD2 gene had an independent and additive effect on cocaine dependence. These findings support a modest role of the DRD3 gene in susceptibility to cocaine dependence.Caine and Koob 1,2 have shown that the pretreatment of rats with the dopamine D 3 agonist 7-OH DPAT shifted the cocaine self-administration dose-effect to the left, suggesting that D 3 receptor stimulation enhances the reinforcing effect of cocaine. Conversely, the self-administration of 7-OH DPAT in rhesus monkeys is modified by prior exposure to cocaine. 3 Some studies in humans also suggest a potential role of the D 3 receptor in cocaine dependence. For example, the D 3 receptor is present in high density in the nucleus accumbens; the prime site of dopamine reward pathway. Its density in this area is two-fold higher in victims of accidental cocaine overdose. 4,5 These observations suggest that cocaine use leads to a neuroadaptive elevation in D 3 receptor density in response to increased synaptic dopamine 6 and that the D 3 receptor may be one mediator of the reinforcing effects of cocaine. 1,2 We hypothesized that if the D 3 receptor plays a role in cocaine dependence, then the DRD3 genotype frequencies might be different in cocaine-dependent individuals than in controls. A MscI (BalI) polymorphism resulting in a substitution of glycine→serine in the first exon of the DRD3 gene has been described by Lannfelt et al. 7 Crocq et al 8 reported a decrease in 12 heterozygosity for this polymorphism and an increase in 11 and 22 homozygosity in subjects with schizophrenia vs controls. Some studies have supported this finding while others have not. In a review of the role of the DRD3 gene in schizophrenia, Asherson et al 9 reported that when they combined their results with those in the literature there was a significant decrease in 12 heterozygosity in males (P = 0.00021) but not in females (P = 0.60), indicative of an important sex effect at this gene in schizophrenia. We have observed a significant decrease in DRD3 MscI 12 heterozygosity in Tourette syndrome 10 and pathological gambling. 11 The studies of Jö nsson et al 12 showed that the mean HVA level for the 11 + 22 DRD3 homozygotes was 190 nmol L −1 compared to 161 nmol L −1 for the 12 heterozygotes (P = 0.0...

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A study of the dopamine D2 receptor gene in pathological gambling

Cited by 287 publications

References 0 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

Association of polymorphisms of dopamine D2 receptor (DRD2), and dopamine transporter (DAT1) genes with schizoid/avoidant behaviors (SAB)

Homozygosity at the dopamine DRD3 receptor gene in cocaine dependence

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