Human brain D1 and D2 dopamine receptors in schizophrenia, Alzheimer's, Parkinson's, and Huntington's diseases.
Because dopamine D2 receptors are known to be elevated in schizophrenic brain striata, this study examined whether a similar dopamine receptor elevation occurred in other diseases including neuroleptic-treated Alzheimer's and Huntington's diseases. The average D1 density in postmortem striata from Alzheimer's patients was 17.6 +/- 0.1 pmol/g, similar to an age-matched control density of 16.6 +/- 0.4 pmol/g. The average D1 density in schizophrenia patients was 19.0 +/- 0.6 pmol/g, similar to the age-matched control density of 17.9 +/- 0.6 pmol/g. In Parkinson's disease patients, however, the D1 receptor density was elevated, with values of 22.8 +/- 1.2 pmol/g (in patients not receiving L-DOPA) and 19.6 +/- 1.5 pmol/g (in patients receiving L-DOPA) compared to the age-matched control density of 16.0 +/- 0.4 pmol/g. The D2 receptors in Alzheimer's striata averaged 13.4 +/- 0.6 pmol/g (in patients who had not received neuroleptics), almost identical to the control density of 12.7 +/- 0.3 pmol/g. The average D2 density in neuroleptic-treated Alzheimer's striata was 16.7 +/- 0.7 pmol/g, an elevation of 31%, the individual values of which had a normal distribution. In Parkinson's disease patients, the D2 densities were elevated in tissues from patients not receiving L-DOPA (19.9 +/- 1.5 pmol/g in putamen and 14.8 +/- 1.2 pmol/g in striatum) compared to the age-matched control values of 13.0 +/- 0.4 pmol/g and 12.6 +/- 0.3 pmol/g, respectively. In Huntington's disease patients, the D2 density averaged 7.5 +/- 0.4 pmol/g in patients who had not received neuroleptics, but was 10.3 +/- 0.6 pmol/g in those who had. Although all of the D1 and D2 densities in each of the above diseases and subgroups revealed a normal distribution pattern, the D2 densities in schizophrenia displayed a bimodal distribution pattern, with 48 striata having a mode at 14 pmol/g, and the other 44 striata having a mode at 26 pmol/g. Thus, compared to the neuroleptic-induced and unimodal elevations in D2 of 31% in Alzheimer's disease and 37% in Huntington's disease, the schizophrenic striata with a mode of 26 pmol/g (105% above control) appear to contain more D2 receptors than can be accounted for by the neuroleptic administration alone.
Seeman
P
P
Department of Pharmacology, University of Toronto, Canada.
Bzowej
N H
NH
Guan
H C
HC
Bergeron
C
C
Reynolds
G P
GP
Bird
E D
ED
Riederer
P
P
Jellinger
K
K
Tourtellotte
W W
WW
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy / Q000378:metabolism*; D008875:Middle Aged; D009928:Organ Specificity; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D011699:Putamen / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012016:Reference Values; D012559:Schizophrenia / Q000378:metabolism*
D014150:Antipsychotic Agents; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2