Centrally mediated opioid induced depression of hepatic glutathione: Effects of intracerebroventricular administration of mu kappa, sigma and delta agonists

Abstract

It has recently been demonstrated that morphine produces a loss of hepatocellular glutathione in mice by virtue of its action within the central nervous system. The ability of opioid receptor antagonists to abolish morphine's effect glutatione suggests that this action is opioid-receptor mediated. The involvement of opioid receptors in this phenomenon is confirmed in the present study in mice by the ability of naltrexone, 100 μg administered intracerebroventricularly (i.c.v),to completely block the decrease in hepatic glutathione induced by an i.c.v. injection of 100 μg of morphine. Intracerebroventricular administration of the selective mu (μ) opioid receptor agonist, (D-Ala2, N-MePhe4, Gly-ol5)enkephalin (DAGO; 25–50 μg), or the selective delta (δ) opioid agonist, [D-Pen2, D-Pen5]enkephalin (DPDPE; 3–50 μg), like morphine, produced significant decreases in hepatic glutathione 3 h after administration. The selective kappa (κ) opioid receptor agonists, ethylketocyclazocine (1–30 μg) and trans-(±)3,4-dichloro-N-methyl- N-[2-(1-pyrrolidinyl)-cyclohexyl]benzenacetamide-methane sufonate (U50 488; 10–300 μg), as well as the selective sigma (gs) opioid agonists, phencyclidine (PCP; 50–300 μx) and N-allylnormetazocine (SKF 10 047; 1–30 μg), had no effect on the concentrations of glutathione ion the liver. It appears from these data that stimulation of μ- or δ-, but not κ- or σ-opioid receptors within the] central nervous system in a loss of hepatocelluclar glutatione