Numerical density of μ opioidreceptor expressing neurons in the frontal cortex of drug related fatalities

In animal and cell culture experiments, chronic morphine treatment has been followed by ‘up’- as well as ‘down-regulation’ of the μ opioidreceptor (μOR) number. The present postmortem morphometric study of morphine-related fatalities of drug addicts ( n=12 and 22–35 years old, with blood unconjugated morphine levels from 27.1 to 458 ng/ml, m.v. 198.5 ng/ml) versus a non-addicted control group ( n=13 and 10–44 years old) was intended to examine whether chronic opiate exposure affects the numerical density of μOR expressing neurons in the human neocortex (area 10 according to Brodmann). For the immunohistochemical procedure, thick (100 μm) vibratome sections were incubated with a monoclonal antibody against the μOR [Arvidsson et al., J. Neurosci. 15 (1995) 3328] and immunoreactive sites were visualized using an immunoperoxidase protocol. The numerical densities of μOR-expressing and Nissl-stained neurons were assessed morphometrically (camera lucida-drawings). In both collectives, the anti-μOR immunoreactivity was mainly found in pyramidal neurons of layers (L) II/III and V and in multiform neurons of L VI. In the drug-related fatalities and the control group, the density of neurons expressing μOR protein was similar, amounting for 2698±153 and 2688±172/mm 3, respectively. These findings extend the binding studies of opioid ligands in postmortem brains of heroin addicts [Gabilondo et al., Psychopharmacology 115 (1994) 135] revealing similar receptor densities and affinities by showing no difference in the density of μOR-positive neurons.