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Ernest P. Noble, PhD, MD; Kenneth Blum, PhD; Terry Ritchie, PhD; Anne Montgomery, MSc; Peter J. Sheridan, PhD

Arch Gen Psychiatry. 1991;48(7):648-654.

Abstract
• 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 nonalcoholic 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 (XhD2G1) of the human D₂ dopamine receptor gene. The binding characteristics (K_d [binding affinity] and B_max [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 K_d 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 B_max was significantly reduced compared with the B_max of subjects with the A2 allele. Moreover, a progressively reduced B_max 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.

Author Affiliations
From the Alcohol Research Center, Neuropsychiatric Institute, and Brain Research Institute, UCLA (Drs Noble and Ritchie), and the Departments of Pharmacology (Dr Blum and Ms Montgomery) and Cellular and Structural Biology (Dr Sheridan), University of Texas Health Science Center, San Antonio.

Footnotes
Accepted for publication April 2, 1991.

Reprint requests to Alcohol Research Center, UCLA Neuropsychiatric Institute, 760 Westwood Plaza, Los Angeles, CA 90024 (Dr Noble). 0000

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