Area-specific increased density of mu-opioid receptor immunoreactive neurons in the cerebral cortex of drug-related fatalities

In animal experiments and in cell culture, chronic morphine treatment has been followed by "up-regulation" as well as "down-regulation" of the mu-opioid receptor (OR) number. The present postmortem morphometric study of morphine-related fatalities of drug-addicts (n=13, 20-35 years old, with blood unconjugated morphine levels from 27.1 ng/ml to 458 ng/ml, m.v. 198.5 ng/ml) versus a non-addicted control group (n=13, 10-44 years old) was intended to examine, whether chronic opiate exposure affects the numerical density of mu-OR expressing neurons in the human neocortex (areas 11, 24 and 25 according to Brodmann). For the immunohistochemical procedure, vibratome sections (100 microm) were incubated with a monoclonal antibody against the mu-OR, diluted 1:100, and immunolabelled sites were visualized using an immunoperoxidase protocol. The numerical densities of OR immunoreactive neuronal profiles and Nissl-stained central profiles were assessed morphometrically (camera lucida-drawings). In both groups, the anti-mu-OR-immunoreactivity was mainly localized in pyramidal neurons of layers (L) II/III and V and in multiform neurons of L VI. In the areas 24 and 25, the density of the immunoreactive neuronal profiles did not display a significant difference between the two examined groups. In the area 11, however, the number of immunolabelled neuronal profiles amounted to 2777+/-206 mm(3) in the drug-related fatalities and to 2320+/-124 mm(3) in the control group and thus was significantly increased.