OPIOID RECEPTOR DENSITY CHANGES IN ALZHEIMER AMYGDALA AND PUTAMEN

Since opioids can influence the release of acetylcholine, substance P and a number of other neurotransmitters that have been implicated in the pathogenesis of Alzheimer's disease (AD), it is of interest to assess opioid receptor levels in AD. We have examined mu, delta and kappa opioid receptor binding parameters, binding sensitivity to a GTP analog and distribution in amygdala, frontal cortex and putamen of AD brain. Control brains were matched according to age, sex, post-mortem interval and storage time. K-d values and GTP analog binding sensitivity did not differ in AD and control brains. B-max values for mu ([H-3]DAMGE) sites also appeared unaffected by in vitro binding assays. In contrast, kappa ([H-3]U69593) and delta ([H-3]DSLET) opioid receptor levels, were significantly changed. In AD amygdala kappa B-max values increased from control levels of 123 +/- 12 to 168 +/- 13 fmol/mg protein, whereas densities of kappa and delta sites were decreased from 94 +/- 8 to 48 +/- 8 and 102 +/- 3.6 to 69 +/- 8.5 fmol/mg protein, respectively, in putamen. Autoradiography revealed corresponding differences in the distribution of kappa opioid receptors. The findings indicate that the kappa binding site, which is quantitatively the major opioid receptor class in human brain, undergoes marked changes in AD amygdala and putamen.