Dopamine receptors and transporters in the brain reward circuits of type 1 and 2 alcoholics measured with human whole hemisphere autoradiography.
The role of the dopamine system in brain reward mechanisms and development of substance abuse is well-established with nucleus accumbens as a key structure in mediating these effects. Several studies on alcoholism have indicated defects in dopaminergic neurotransmission and alterations in dopamine receptor densities. However, it has remained unclear if the substance abuse-related dopaminergic defect is specifically associated with a certain receptor subtype. The aim of this study was to compare putative alterations of dopamine D(1,) D(2), and D(3) receptors in nucleus accumbens, amygdala, and substantia nigra among alcoholics and controls. We studied the densities of dopamine D(1) and D(3) receptors in brains of 9 type 1 alcoholics, 8 type 2 alcoholics, and 10 healthy controls by using postmortem human whole hemisphere autoradiography. The mean densities of dopamine D(1) and D(3) receptors were at the same level in all study groups. Combining these with our previous results, our data suggest that among type 1 alcoholics dopamine transporters are lower in nucleus accumbens and dopamine D(2), but not D(1) or D(3) receptors in nucleus accumbens and amygdala. Further, the densities of all these dopamine-binding sites among type 2 alcoholics are at the level of healthy controls. The results suggest that lower dopamine receptor density is specific for D(2) receptor and for type 1 alcoholism, which supports Cloninger's neurogenetic model of two alcoholic subtypes, and indicates the importance of classifying these subgroups separately when issues related to dopaminergic activity are studied.
Tupala
Erkki
E
Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Kuopio, Finland. erkki.tupala@niuva.fi
Hall
Håkan
H
Mantere
Tuija
T
Räsänen
Pirkko
P
Särkioja
Terttu
T
Tiihonen
Jari
J
D000328:Adult; D017668:Age of Onset; D000437:Alcoholism / Q000453:epidemiology* / Q000378:metabolism*; D000679:Amygdala / Q000378:metabolism; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D009434:Neural Pathways / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D012201:Reward; D013378:Substantia Nigra / Q000378:metabolism; D014018:Tissue Distribution
C493593:DRD3 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3