INHIBITION OF MORPHINE-TOLERANCE AND DEPENDENCE BY DIAZEPAM AND ITS RELATION TO CNS OPIOID-PEPTIDES

Daily injections of diazepam (0.025-2.5 mg/kg) inhibited tolerance to antinociception in rats implanted with morphine pellets, Diazepam admi nistration (0.25 mg/kg) also decreased the degree of jumping behavior observed following naloxone injection in morphine pellet implanted rat s. Met-enkephalin levels decreased in the hypothalamus and spinal cord of morphine tolerant-dependent rats and in the hypothalamus, hippocam pus, cortex and spinal cord of abstinent rats. Diazepam treatment reve rsed this decrease in the met-enkephalin levels in both tolerant-depen dent acid abstinent animals. Diazepam treatment also enhanced beta-end orphin 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 mo rphine tolerance and dependence.