BLOCKADE OF MORPHINE ANALGESIA BY AN ANTISENSE OLIGODEOXYNUCLEOTIDE AGAINST THE MU-RECEPTOR

The recent cloning of mu, delta and kappa(1) opioid receptors has prov ided opportunities in the study of their pharmacology. Using an antise nse strategy developed against delta and kappa(1) opioid receptors, we designed an antisense oligodeoxynucleotide directed against the 5'-un translated region of MOR-1 clone, 51-70 bp upstream from the initiatin g ATG. Microinjection of this antisense oligodeoxynucleotide directly into the periaqueductal gray on Days 1, 3 and 5 completely blocked the analgesic actions of morphine administered into the periaqueductal gr ay on Day 6 (p < 0.001), 24 hr after the last antisense treatment. Rat s treated with vehicle or with a mismatch oligodeoxynucleotide in whic h two pairs of bases from the antisense sequence had been switched wer e not significantly affected. These findings confirm the pharmacologic al relevance of the MOR-1 clone and its involvement in morphine's acti ons.