MU-OPIOID RECEPTOR AND ALPHA(2)-ADRENOCEPTOR AGONIST BINDING-SITES INTHE POSTMORTEM BRAIN OF HEROIN-ADDICTS

The biochemical status of human brain mu-opioid receptors and az-adren oceptors during opiate dependence was studied by means of the binding of [H-3] [D-Ala(2), MePhe(4) Gly-ol(5)] enkephalin (DAGO) and [H-3]clo nidine, respectively, in postmortem brains of heroin addicts who had d ied by opiate overdose or other causes. In the frontal cortex, thalamu s and caudate of heroin addicts the density (B-max) and affinity (K-D) of mu-opioid receptors were similar to those in controls. In contrast , the density of alpha(2)-adrenoceptors in heroin addicts was found to be significantly decreased in frontal cortex (B-max 31% lower), hypot halamus (B-max 40% lower) and caudate (B-max 32% lower) without change s in K-D values. When heroin addicts were divided into two subgroups a ccording to the presence or absence of morphine in body fluids, only t he group with positive screening for morphine showed relevant decrease s in brain alpha(2)-adrenoceptor density (B-max 36-48% lower), whereas the decreases in receptor density observed in the subgroup with negat ive screening for morphine did not reach statistical significance. The results suggest that desensitization of brain alpha(2A)-adrenceptors is a relevant adaptative receptor mechanism during opiate addiction in humans.