G-PROTEIN ANTISENSE OLIGO DEOXYRIBONUCLEOTIDES AND MU-OPIOID SUPRASPINAL ANTINOCICEPTION

The present study utilized an in vivo antisense strategy to examine the functional interaction of supraspinal mu-opioid receptors with the G protein subunits G(i)1 alpha, G(i)2 alpha, G(i)3 alpha and G(s) alpha. Mice were injected intracerebroventricularly (i.c.v.) with 33-base phosphorothioate oligodeoxyribonucleotides (12.5 mu g) or with vehicle in equal volume (sterile water, 5 mu l) and the antinociceptive responses to i.c.v. morphine, [D-Ala(2),NMePhe(4),Gly(5)-ol]enkephalin (DAMGO) or sufentanil were determined 18-24 h later using the tail-flick test. Treatment with antisense to G(i)2 alpha, but not the other subunits, significantly attenuated morphine-induced antinociception. The degree of attenuation for the three mu-opioid agonists was in the order morphine > DAMGO > sufentanil, the inverse of their intrinsic efficacy.