Effects of morphine on monosodium glutamate neurotoxicity and its mechanism

The enhancing effects of morphine on monosodium glutamate (MSG) neurotoxicity and its blocking by naloxone were studied through morphological observation, together with detection of concentrations of intracellular free Ca2+ (Ca2+]i) by Ca2+ indicator Fura-2/AM and lactate dehydrogenase (LDH) efflux in the bathing medium in primary cultures from 14-17 d old mouse fetal cortex. It was found that 10 min pre-incubation of young cortical neurons (7 day in vitro) with morphine 10(-7) or 10(-6) mol.L-1 substantially increased LDH release from 105.7% +/- 19.0% (treated with MSG alone) to 194.5% +/- 17.7% and 214.0% +/- 9.5% respectively after exposure to MSG 0.1 mmol.L-1, but pre-incubation with morphine (10(-7) or 10(-6) mol.L-1) plus naloxone (0.1 mmol.L-1) reversed the LDH release after treatment with the same concentration of MSG. Morphine (10(-7) or 10(-6) mol.L-1) produced little elevation of Ca2+]i. However, when combined with MSG (0.1 mmol.L-1) morphine elevated the Ca2+]i level much more than MSG alone. These results suggest that morphine markedly enhances excitotoxic neuron damage, which can be reversed by naloxone. Overloading of intracellular Ca2+ may be a simultaneous pathological mechanism underlying the neuronal damage and death that occur in excitatory toxicity.