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 alpha 2-adrenoceptors during opiate dependence was studied by means of the binding of [3H] [D-Ala2, MePhe4, Gly-ol5] enkephalin (DAGO) and [3H]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 (Bmax) and affinity (KD) 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 (Bmax 31% lower), hypothalamus (Bmax 40% lower) and caudate (Bmax 32% lower) without changes in KD 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 (Bmax 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.