Dopamine Receptor D4 Polymorphism Predicts the Effect of L-DOPA on Gambling Behavior

• Published in: Biological psychiatry (1969) Vol. 67; no. 8; pp. 702 - 706
• Main Authors: Eisenegger, Christoph, Knoch, Daria, Ebstein, Richard P., Gianotti, Lorena R.R., Sándor, Peter S., Fehr, Ernst
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.04.2010; Elsevier
• Subjects: Adult; Adult and adolescent clinical studies; Biological and medical sciences; Decision making; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; dopamine; Dopamine Agents - adverse effects; Dopamine Agents - pharmacokinetics; Dopamine Agents - pharmacology; Double-Blind Method; Gambling - psychology; Genotype; Humans; impulse control disorder; Impulsive Behavior - psychology; Levodopa - adverse effects; Levodopa - pharmacokinetics; Levodopa - pharmacology; Male; Medical sciences; Miscellaneous; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Organic mental disorders. Neuropsychology; Parkinson's disease; pathological gambling; pharmacogenetics; Polymorphism, Genetic; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Receptors, Dopamine D4 - drug effects; Receptors, Dopamine D4 - genetics; Reverse Transcriptase Polymerase Chain Reaction; Young Adult; impulse control disorder; Parkinson's disease; pathological gambling; Decision making; dopamine; pharmacogenetics; Agonist; Impulse control disorder; Parkinson disease; Genetic determinism; Pathological gambling; Genetics; Degenerative disease; Behavior; Levodopa; Nervous system diseases; Pharmacogenetics; Dopamine; Dopamine receptor; Catecholamine; Gambling game; Antiparkinson agent; Cerebral disorder; D2 Dopamine receptor; Central nervous system disease; Neurotransmitter; Predictive factor; Extrapyramidal syndrome; Polymorphism
• ISSN: 0006-3223; 1873-2402; 1873-2402
• DOI: 10.1016/j.biopsych.2009.09.021

There is ample evidence that a subgroup of Parkinson's disease patients who are treated with dopaminergic drugs develop certain behavioral addictions such as pathological gambling. The fact that only a subgroup of these patients develops pathological gambling suggests an interaction between dopaminergic drug treatment and individual susceptibility factors. These are potentially of genetic origin, since research in healthy subjects suggests that vulnerability for pathological gambling may be linked to variation in the dopamine receptor D4 (DRD4) gene. Using a pharmacogenetic approach, we investigated how variation in this gene modulates the impact of dopaminergic stimulation on gambling behavior in healthy subjects. We administered 300 mg of L-dihydroxyphenylalanine (L-DOPA) or placebo to 200 healthy male subjects who were all genotyped for their DRD4 polymorphism. Subjects played a gambling task 60 minutes after L-DOPA administration. Without considering genetic information, L-DOPA administration did not lead to an increase in gambling propensity compared with placebo. As expected, however, an individual's DRD4 polymorphism accounted for variation in gambling behavior after the administration of L-DOPA. Subjects who carry at least one copy of the 7-repeat allele showed an increased gambling propensity after dopaminergic stimulation. These findings demonstrate that genetic variation in the DRD4 gene determines an individual's gambling behavior in response to a dopaminergic drug challenge. They may have implications for the treatment of Parkinson's disease patients by offering a genotype approach for determining individual susceptibilities for pathological gambling and may also afford insights into the vulnerability mechanisms underlying addictive behavior.