Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism

Journal Article · Mon Jul 01 04:00:00 EDT 1991 · Archives of General Psychiatry; (United States)

DOI:https://doi.org/10.1001/archpsyc.1991.01810310066012· OSTI ID:5388120

Noble, E P; Blum, K; Ritchie, T; Montgomery, A; Sheridan, P J ^[1]

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1. Neuropsychiatric Institute, UCLA (USA)

The allelic association of the human D2 dopamine receptor gene with the binding characteristics of the D2 dopamine receptor was determined in 66 brains of alcoholic and non-alcoholic subjects. In a blinded experiment, DNA from the cerebral cortex was treated with the restriction endonuclease Taql and probed with a 1.5-kilobase (kb) digest of a clone (lambda hD2G1) of the human D2 dopamine receptor gene. The binding characteristics (Kd (binding affinity) and Bmax (number of binding sites)) of the D2 dopamine receptor were determined in the caudate nuclei of these brains using tritiated spiperone as the ligand. The adjusted Kd was significantly lower in alcoholic than in nonalcoholic subjects. In subjects with the A1 allele, in whom a high association with alcoholism was found, the Bmax was significantly reduced compared with the Bmax of subjects with the A2 allele. Moreover, a progressively reduced Bmax was found in subjects with A2/A2, A1/A2, and A1/A1 alleles, with subjects with A2/A2 having the highest mean values, and subjects with A1/A1, the lowest. The polymorphic pattern of the D2 dopamine receptor gene and its differential expression of receptors suggests the involvement of the dopaminergic system in conferring susceptibility to at least one subtype of severe alcoholism.

• OSTI ID: 5388120
• Journal Information: Archives of General Psychiatry; (United States), Journal Name: Archives of General Psychiatry; (United States) Vol. 48:7; ISSN ARGPA; ISSN 0003-990X
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
DNA
DNA-ASE
DOPAMINE
DRUGS
ENDONUCLEASES
ENZYMES
ESTERASES
ETHANOL
GENE REGULATION
GENES
HYDROGEN COMPOUNDS
HYDROLASES
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LIGANDS
MAMMALS
MAN
MEMBRANE PROTEINS
METABOLISM
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PHENOLS
PHOSPHODIESTERASES
POLYPHENOLS
PRIMATES
PROTEINS
REACTION KINETICS
RECEPTORS
SPIPERONE
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES