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

Abstract

In animal experiments and in cell culture, chronic morphine treatment has been followed by “up-regulation” as well as “down-regulation” of the μ-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 μ-OR expressing neurons in the human neocortex (areas 11, 24 and 25 according to Brodmann). For the immunohistochemical procedure, vibratome sections (100 μm) were incubated with a monoclonal antibody against the μ-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-μ-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.