Opioid receptor density changes in Alzheimer amygdala and putamen

Since opioids can influence the release of acetylcholine, substance P and a number of other neurotransmitter 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 μ, δ and κ 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 internal and storage time. K d values and GTP analog binding sensitivity did not differ in AD and control brains. B max values for μ ([ 3H]DAMGE) sites also appeared unaffected by in vitro binding assays. In contrast, κ ([ 3H]U69593) and δ ([ 3H]DSLET) opioid receptor levels, were significantly changed. In AD amygdala κ B max values increased from control levels of 123 ± 12 to 168 ± 13fmol/mg protein, whereas densities of κ and δ sites were decreased from > 94 ± 8 to 48 ± 8 and 102 ± 3.6 to 69 ± 8.5fmol/mg protein, respectively, in putamen. Autoradiography revealed corresponding differences in the distribution of κ opioid receptors. The findings indicated that the κ binding site, which is quantitatively the major opioid receptor class in human brain, undergoes marked changes in AD amygdala and putamen.