Organization of dopamine D1 and D2 receptors in human striatum: receptor autoradiographic studies in Huntington's disease and schizophrenia.
The technique of quantitative autoradiography was used to examine the effects of Huntington's disease (HD) and schizophrenia on the organization of striatal dopamine (DA) D1 and D2 receptors. Whereas the striatum of HD cases showed a reduction in the density of D1 ([3H]SCH 23390) and D2 ([3H]spiroperidol) receptors, the patterning of D2 receptor loss did not match that of the D1 receptor loss. The HD loss of D1 D1 receptors (65%) is far greater than the loss of D2 receptors (28%). Whereas there was a dorsal-ventral gradient of effect on both receptor subtypes, the effects of HD on D2 receptors in the ventral putamen (PUT) and nucleus accumben septi (NAS) were minimal. Similarly, muscarinic M1 and M2 receptors demonstrate different patterns of alteration in HD. The M2 subtype, labeled with [3H]N-methylscopolamine (in the presence of excess pirenzepine to occlude M1 sites), was depleted far more than the M1 receptor subtype, labeled with [3H]pirenzepine. Although the effects of HD on [3H]mazindol labeling of DA terminals were more heterogeneous, there appeared to be a relative preservation of this afferent input to the striatum of the HD cases. In the schizophrenic cases, our autoradiographic studies confirm previous reports of an elevation of D2 receptor density in the striata of many schizophrenics. This increase was evident even though two of the three cases were known to have not been treated with neuroleptics, and the third case may also have been drug naive. However, the increase was far greater in the NAS (164%) and ventral PUT (173%) than more dorsally in the striatum (68%). The density of D1 receptors and DA terminals labeled with [3H]mazindol in the striatum of schizophrenics was not significantly different from that of control cases. Thus in both HD and schizophrenia, the ratio of D2/D1 receptors is altered in favor of the D2 population, particularly in the NAS.
Joyce
J N
JN
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia 19104-6048.
Lexow
N
N
Bird
E
E
Winokur
A
A
D000368:Aged; D001345:Autoradiography; D001552:Benzazepines / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011954:Receptors, Dopamine / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism
D001552:Benzazepines; D011954:Receptors, Dopamine; D013134:Spiperone