D-2 DOPAMINE-RECEPTOR POLYMORPHISM AND BRAIN REGIONAL GLUCOSE-METABOLISM

Positron emission tomography (PET) studies have shown decreased glucos e metabolism in brain regions of detoxified alcoholics and cocaine abu sers, However, it is not clear whether this decrease is due to chronic drug abuse or a pre-existing condition, Molecular genetic studies hav e found an association of the D-2 dopamine receptor (DRD2) A1 allele w ith alcoholism and drug abuse, Moreover, reduced central dopaminergic function has been suggested in subjects who carry the A1 allele (A1(+) ) compared with those who do not (A1(-)), In the present study, using F-18- deoxyglucose, regional glucose metabolism was determined in heal thy nonalcohol/nondrug-abusing subjects with the A1(+) or A1(-) allele , The mean relative glucose metabolic rate (GMR) was significantly low er in the A1(+) than the A1(-) group in many brain regions, including the putamen, nucleus accumbens, frontal and temporal gyri and medial p refrontal, occipito-temporal and orbital cortices, Decreased relative GMR in the A1(+) group was also found in Broca's area, anterior insula , hippocampus, and substantia nigra, A few brain areas, however, showe d increased relative GMR in the A1(+) group, Since polymorphism of the DRD2 gene is commonly observed in humans, the importance of different iating A1(+) and A1(-) alleles subjects in PET studies is suggested, ( C) 1997 Wiley-Liss, Inc.