CHRONIC NALTREXONE DIFFERENTIALLY AFFECTS SUPRASPINAL DELTA-OPIOID RECEPTOR-MEDIATED ANTINOCICEPTION

The effects of chronic treatment with naltrexone, an opioid receptor a ntagonist, on delta(1)- and delta(2)-opioid receptor agonist-induced a ntinociception and ligand binding were investigated in mice. Antinocic eption by intracerebroventricular (i.c.v.) [D-Pen(25)]enkephalin (DPDP E) and [D-Ala(2)]deltorphin II, agonists selective for delta(1)- and d elta(2)-opioid receptors, respectively, was blocked following subcutan eous (s.c.) implantation of a naltrexone pellet (7.5 mg) for 7 days. R emoval of the naltrexone pellet was followed 24 h later by a decrease of 7.5-fold in the ED50 value of [D-Ala(2)]deltorphin II, but not that of DPDPE. In a whole brain homogenate the binding of [H-3][D-Ala(2)]d eltorphin II was increased twice as much as that of [H-3]DPDPE. Chroni c naltrexone treatment also produced an 8.6-fold decrease in the ED50 value of i.c.v. administered morphine. The increase in morphine potenc y was reversed to a control (placebo-treated mice) value by the select ive delta(2)-opioid receptor antagonist, naltriben (25 pmol, i.c.v.). Thus, chronic naltrexone selectively increases delta(2)-opioid recepto r-mediated antinociception, supporting the existence of delta opioid r eceptor subtypes with distinct adaptive characteristics. The data also indicate that delta(2)-opioid receptors are critically involved in th e expression of morphine supersensitivity. (C) 1998 Elsevier Science B .V.