Inhibition of morphine tolerance and dependence by diazepam and it's relation to CNS opioid peptides

Abstract

Daily injections of diazepam (0.025–2.5 mg/kg) inhibited tolerance to antinociception in rats implanted with morphine pellets. Diazepam administration (0.25 mg/kg) also decreased the degree of jumping behavior observed following naloxone injection in morphine pellet implanted rats. Met-enkephalin levels decreased in the hypothalamus and spinal cord of morphine tolerant-dependent rats and in the hypothalamus, hippocampus, cortex and spinal cord of abstinent rats. Diazepam treatment reversed this decrease in the met-enkephalin levels in both tolerant-dependent and abstinent animals. Diazepam treatment also enhanced β-endorphin levels in hypothalamus and spinal cord, and dynorphin levels in the pons/medulla of morphine treated animals during abstinence. These results implicate met-enkephalin in diazepam induced inhibition of morphine tolerance and dependence.