EFFECTS OF INTRACEREBROVENTRICULAR ADMINISTRATION OF BETA-FUNALTREXAMINE ON DAMGO-STIMULATED [S-35] GTP-GAMMA-S BINDING IN RAT-BRAIN SECTIONS

Intracerebroventricular administration of beta-funaltrexamine (beta-FN A) reduces the density of mu opioid receptors as measured by in situ a utoradiography by 40-50% throughout the brain, with little regional va riation [Martin et al. (1993) J. Pharmacol. Exp. Ther. 267:506-514] Re cently an assay has been developed to study opioid stimulation of [S-3 5]GTP-gamma-S binding autoradiographically in situ using slide-mounted brain sections [Sim et al. (1995) Proc. Natl. Acad. Sci. U.S.A. 92:72 42-7246]. The present study was undertaken to determine the effect of mu opioid receptor alkylation on G protein activation by the mu opioid agonist DAMGO. Animals were injected intracerebroventricularly with 4 0 nmol of beta-FNA or saline and sacrificed 24 hours later. DAMGO stim ulated [S-35]GTP-gamma-S binding with an anatomical specificity consis tent with the localization of mu opioid receptors. The percent stimula tion by DAMGO ranged from similar to 50 to 100% in the regions studied . beta-FNA significantly decreased G protein activation by DAMGO in re gions that are consistent with its reported long-lasting and insurmoun table antagonism of the antinociceptive (medial thalamus, central gray ) and reinforcing (nucleus accumbens) effects of mu opioid agonists [A dams et al. (1990) J. Pharmacol. Exp. Ther. 255:1027-1032; Martin et a l. (1995) J. Pharmacol. Exp. Ther. 272:1135-1140]. However, the effect s of beta-FNA were not equal in all brain regions. This may indicate r egional differences in the coupling efficiency of mu opioid receptors with G proteins, or in the effects of beta-FNA on mu opioid receptor b inding or on mu opioid receptor-stimulated G protein activity. (C) 199 7 Wiley-Liss, Inc.