ANTISENSE OLIGODEOXYNUCLEOTIDE TO DELTA-OPIOID RECEPTORS ATTENUATES MORPHINE-DEPENDENCE IN MICE

The effect of intracerebroventricular treatment with antisense oligode oxynucleotide (A-oligo) to delta opioid receptor mRNA on the morphine- induced place preference and naloxone-precipitated jumping was examine d in morphine-dependent mice. Morphine (5 mg/kg, s.c.) produced a sign ificant place preference. I.c.v. pretreatment with A-oligo (0.01-1 mu g/mouse) dose-dependently attenuated this morphine (5 mg/kg, s.c.)-ind uced place preference, while mismatched oligodeoxynucleotide (M-oligo; 1 mu g/mouse, i.c.v.) was ineffective. Naloxone (3 mg/kg, s.c.) preci pitated jumping in morphine-dependent mice. I.c.v. pretreatment with A -oligo (1 mu g/mouse) attenuated this naloxone (3 mg/kg, s.c.)-precipi tated jumping in morphine-dependent mice, while M-oligo (1 mu g/mouse, i.c.v.) was ineffective. These data demonstrate that the selective re duction in supraspinal delta opioid receptor function caused by pretre atment with A-oligo attenuated the morphine-induced place preference a nd naloxone-precipitated jumping in morphine-dependent mice, suggestin g that the rewarding effect of and physical dependence on morphine may be modulated by central delta opioid receptors. (C) 1997 Elsevier Sci ence Inc.