ENHANCED KAPPA-OPIOID RECEPTOR-MEDIATED ANALGESIA BY ANTISENSE TARGETING THE SIGMA(1) RECEPTOR

In the current study, we used an antisense oligodeoxynucleotide target ing the recently cloned sigma(1) receptor to assess its functions with in the nervous system. sigma(1) antagonists potentiate the analgesic a ctions of opioids. Similarly, the antisense probe targeting the sigma( 1) receptor enhanced the analgesic activity of the kappa(1)-opioid rec eptor agonist U50,488H ro-N[2-(1-pyrrolidinyl)cyclohexyl]benzeacetamid el) and the kappa(3)-opioid receptor agonist naloxone benzoylhydrazone . A mismatch control was inactive. These results confirm the role of s igma(1) receptors in an anti-opioid analgesic system and illustrate th e utility of antisense approaches towards the elucidation of sigma rec eptor functions. (C) 1997 Elsevier Science B.V.