Enhanced kappa-opioid receptor-mediated analgesia by antisense targeting the sigma(1) receptor

In the current study, we used an antisense oligodeoxynucleotide targeting the recently cloned sigma(1) receptor to assess its functions within the nervous system. sigma(1) antagonists potentiate the analgesic actions of opioids. Similarly, the antisense probe targeting the sigma(1) receptor enhanced the analgesic activity of the kappa(1)-opioid receptor agonist U50,488H (trans-3,4-dichloro-N[2-(1-pyrrolidinyl)cyclohexyl]benzeacetamidel) and the kappa(3)-opioid receptor agonist naloxone benzoylhydrazone. A mismatch control was inactive. These results confirm the role of sigma(1) receptors in an anti-opioid analgesic system and illustrate the utility of antisense approaches towards the elucidation of sigma receptor functions. (C) 1997 Elsevier Science B.V.