The effects of antisense to G on opioid agonist potency and G

Ž . Ž . In this study, mice received a single intracerebroventricular i.c.v. injection of an antisense oligodeoxynucleotide ODN directed towards the mRNA of G . Controls received a saline or a nonsense ODN injection. The subsequent effects on protein levels and mRNA ia 2 Žw 2 5x . of G were determined in mouse striatum, as well as, the effect on opioid D-Ala , D-Leu -enkephalin; DADLE inhibition of cyclic ia 2 Ž . Ž . AMP cAMP formation in striatum and morphine analgesic potency. At 48 h after treatment, maximal inhibition E of cAMP max formation was significantly reduced for the antisense group compared to controls. Antisense ODN treatment only changed the E and max did not significantly alter the IC s of the dose–effect curves for inhibition of cAMP formation. Antisense ODN, but not nonsense ODN, 50 significantly reduced morphine’s analgesic potency by )2-fold, 48 h following treatment. Using a quantitative immunoblotting procedure, antisense treatment was shown to decrease striatal G protein 48 h after antisense injection, while there were no changes in ia 2 protein levels at 2, 12 and 24 h. In contrast, no changes in G mRNA in mouse striatum were noted at any time after antisense ia 2 treatment. Taken together, these data suggest that G mediates opioid-induced analgesia and opioid inhibition of cAMP production in ia 2 the mouse. These data also suggest that antisense reduces target protein by a mechanism independent of changes in mRNA abundance. q 1998 Elsevier Science B.V. All rights reserved.