Decreases in dopamine receptors but not in dopamine transporters in alcoholics.
It has been hypothesized that ethanol's actions on the dopamine (DA) system may participate in addiction. The purpose of this study was to evaluate the DA system in the brain of alcoholics. We evaluated 10 alcoholics and 17 nonalcoholics using positron emission tomography and [11C]raclopride to measure DA D2 receptors. In addition, in 5 of the alcoholics and 16 of the nonalcoholics, we also measured DA transporters with [11C]d-threo methylphenidate. The ratio of the distribution volumes in striatum to that in cerebellum, which corresponds to Bmax/Kd + 1, was used as model parameter of DA D2 receptor and transporter availability. Dopamine D2 receptor availability (Bmax/Kd) was significantly lower in alcoholics (2.1 +/- 0.5) than in nonalcoholics (2.7 +/- 0.6) (p < 0.05) and was not correlated with days since last alcohol use. Alcoholics showed DA transporter values similar to those in nonalcoholics. The ratio of DA D2 receptor to transporter availability was significantly higher in nonalcoholics (1.4 +/- 0.1) than in alcoholics (1.1 +/- 0.1) (p < 0.005). Alcoholics showed significant reductions in D2 receptors (postsynaptic marker) but not in DA transporter availability (presynaptic marker) when compared with nonalcoholics. Because D2 receptors in striatum are mainly localized in gamma-aminobutyric acid (GABA) cells these results provide evidence of GABAergic involvement in the dopaminergic abnormalities seen in alcoholics.
Volkow
N D
ND
Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
Wang
G J
GJ
Fowler
J S
JS
Logan
J
J
Hitzemann
R
R
Ding
Y S
YS
Pappas
N
N
Shea
C
C
Piscani
K
K
D000328:Adult; D000428:Alcohol Drinking; D000437:Alcoholism / Q000000981:diagnostic imaging / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008774:Methylphenidate; D009419:Nerve Tissue Proteins; D020891:Raclopride; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D012457:Salicylamides; D014055:Tomography, Emission-Computed; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011954:Receptors, Dopamine; D012457:Salicylamides; D008774:Methylphenidate; D000431:Ethanol; D020891:Raclopride; D005680:gamma-Aminobutyric Acid; D004298:Dopamine