Mu-, delta- and kappa-opioid receptor populations are differentially altered in distinct areas of postmortem brains of Alzheimer's disease patients.
The putative role of the opioid system in cognitive and memory functions prompted us to search for possible changes in the cohort of the major opioid receptors, mu, delta and kappa, in Alzheimer's disease. The present study examines alterations in opioid receptor levels by quantitative autoradiography. These experiments were carried out on coronal sections of postmortem brains from Alzheimer's disease patients and from aged-matched, dementia-free individuals. Brain sections were labeled with the tritiated forms of mu-, delta- and kappa-opioid ligands; DAMGO ([D-Ala(2),N-Me-Phe(4),Gly-ol(5)]-enkephalin), DPDPE ([D-Pen2,5]-enkephalin) and bremazocine (in the presence of mu- and delta-ligands), respectively. Nonspecific binding was determined in the presence of naloxone (10 microM). Brain areas analyzed were caudate, putamen, amygdaloid complex, hippocampal formation and various cerebral and cerebellar cortices. Image analyses of autoradiographs show, that in comparison to the same areas in control brain, statistically significant reductions in mu-opioid receptor binding occur in the subiculum and hippocampus of Alzheimer's disease brains. Binding of delta-opioid receptors is also decreased in the amygdaloid complex and ventral putamen of Alzheimer's disease brains. In contrast, large increases of kappa-opioid receptor binding are found in the dorsal and ventral putamen as well as in the cerebellar cortex of Alzheimer's disease brains. Levels of mu- delta- and kappa-opioid receptor binding are unaltered in the caudate, parahippocampal gyrus and occipito-temporal gyrus. These results may suggest an involvement of the endogenous opioid system in some of the multitude of effects that accompany this dementia.
The Rockefeller University, Laboratory of the Biology of Addictive Diseases, 1230 York Avenue, New York, NY 10021, USA.
A M
AM
Mathieu-Kia
L Q
LQ
Fan
M J
MJ
Kreek
E J
EJ
Simon
J M
JM
Hiller
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001345:Autoradiography; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D003720:Densitometry; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D014316:Tritium
D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D014316:Tritium