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

The biochemical status of human brain mu-opioid receptors and az-adrenoceptors 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]clonidine, respectively, in postmortem brains of heroin addicts who had died by opiate overdose or other causes. In the frontal cortex, thalamus 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), hypothalamus (B-max 40% lower) and caudate (B-max 32% lower) without changes in K-D values. When heroin addicts were divided into two subgroups according to the presence or absence of morphine in body fluids, only the group with positive screening for morphine showed relevant decreases in brain alpha(2)-adrenoceptor density (B-max 36-48% lower), whereas the decreases in receptor density observed in the subgroup with negative 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.