A NONPEPTIDIC DELTA-OPIOID RECEPTOR AGONIST, BW373U86, ATTENUATES THEDEVELOPMENT AND EXPRESSION OF MORPHINE ABSTINENCE PRECIPITATED BY NALOXONE IN RAT

The effect of (+/-)-4-((alpha-R)-alpha-((2S*, i-perazinyl)-3-hydroxyb enzyl)-N,N-diethylbenzamide (BW373U86), the first potent nonpeptidic, highly selective delta opioid receptor agonist, on morphine dependence was studied in rats. Continuous infusion of BW373U86 by a subcutaneou sly implanted osmotic minipump did not induce any abnormal behavior. A fter 6 days of BW373U86 infusion, intraperitoneal injection of a high dose of naloxone or naltrindole did not precipitate morphine-like abst inence syndromes. Furthermore, a single injection of BW373U86 did not induce abstinence syndromes or modulate morphine abstinence precipitat ed by naloxone in chronic morphine-treated rats. However, naloxone-pre cipitated abstinence syndromes in morphine-dependent rats were partial ly suppressed by BW373U86 in a dose-dependent manner when the compound was infused subcutaneously before and throughout morphine treatment. Abstinence signs such as wet-dog shake, forelimb tremor and teeth chat tering were either suppressed or the intensity was significantly atten uated in these BW373U86-infused rats. This effect was antagonized by n altrindole. These data show that chronic infusion of BW373U86 does not produce physical dependence and that it attenuates some abstinence be haviors in morphine-dependent rats via delta opioid receptors.