BLOCKADE OF MORPHINE SUPERSENSITIVITY BY AN ANTISENSE OLIGODEOXYNUCLEOTIDE TARGETING THE DELTA-OPIOID RECEPTOR (DOR-1)

An antisense oligodeoxynucleotide (ODN) targeting 20 bases of the codi ng sequence of the cloned delta opioid receptor (DOR-1), a mismatched ODN (different from the antisense ODN at 4 bases) or saline was admini stered to 3 groups of CD-1 mice implanted with naltrexone pellets (7.5 mg) for 7 days. Morphine supersensitivity (i.e., increased potency as defined by decreased morphine ED(50) values) was observed 24 h after pellet removal (day 8) in mice treated with saline or mismatch ODN, bu t not in antisense ODN treated mice. Antisense ODN alone had no effect on basal nociceptive thresholds or morphine analgesia but reduced the analgesic potency of the delta(2) opioid agonist [D-Ala(2)]deltorphin II. These data suggest that the delta, opioid receptor system partici pates in the adaptive changes contributing to increased morphine poten cy following chronic naltrexone treatment.