Blockade of morphine analgesia by an antisense oligodeoxynucleotide against the mu receptor.

The recent cloning of mu, delta and kappa 1 opioid receptors has provide opportunities in the study of their pharmacology. Using an antisense strategy developed against delta and kappa 1 opioid receptors, we designed an antisense oligodeoxynucleotide directed against the 5'-untranslated region of MOR-1 clone, 51-70 bp upstream from the initiating 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 gray on Day 6 (p < 0.001), 24 hr after the last antisense treatment. Rats treated with vehicle or with a mismatch oligodeoxynucleotide in which two pairs of bases from the antisense sequence had been switched were not significantly affected. These findings confirm the pharmacological relevance of the MOR-1 clone and its involvement in morphine's actions.