EFFECTS OF MORPHINE ON MONOSODIUM GLUTAMATE NEUROTOXICITY AND ITS MECHANISM

The enhancing effects of morphine on monosodium glutamate (MSG) neurtotoxicity and its blocking by naloxone were studied through morphological observation,together with detectionof concentrations of intracellular free Ca²⁺(Ca²⁺i) by Ca²⁺ indicator Fura-2/AM and lactatedehydrogenase (LDH)efflux in the bathing medium in primary cultures from 14～17 d old mouse fetalcortex, it was found that 10 min pre-incubation of young cortical neurons(7 day in,vitro )withmorphine 10-7 or 10-6mol·L^-1 substantially increased LDH release from 105.7%±19.0%(treatedwith MSG alone)to l94.5%±17.7%and 214.0%±9.5%respectively after exposure to MSG0.1mmol·L^-1, but pre-incubation with morphine(10-7 or10-6 mol·L^-1)plus naloxone (0.1mmol·L-1) reversed the LDH release after treatment with the same concentration of MSG. Morphine(10-7 or 1O-6 mol·L^-1) produced little elevation ofCa²⁺i. However, when combined with MSG(0.1 mmol·L^-1) morphine elevated theCa²⁺i level much more than MSG alone, These resultssuggest that morphine markedly enhances excitotoxic neuron damage, which can be reversed bynaloxone. Overloading of intracellular Ca²⁺ may be a simultaneous pathological mechanismunderlying the neuronal damage and death that occur in excitatory toxicity.