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[Effects of morphine on monosodium glutamate neurotoxicity and its mechanism]
Abstract:
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.
Insights
Morphine amplifies excitotoxicity in neurons, increasing cell damage and death. This harmful effect is blocked by naloxone, suggesting a potential therapeutic target for neuroprotection.
Area of Science:
- Neuroscience
- Neuropharmacology
- Cell Biology
Context:
- Investigating the role of opioids in neuronal damage.
- Examining the mechanisms of excitotoxicity in primary neuronal cultures.
- Assessing the impact of morphine and naloxone on neuronal health.
Purpose:
- To determine if morphine enhances monosodium glutamate (MSG)-induced neurotoxicity.
- To investigate the role of intracellular calcium (Ca2+) in morphine-potentiated excitotoxicity.
- To evaluate the neuroprotective effect of naloxone against morphine-enhanced excitotoxicity.
Summary:
- Morphine (10(-7) - 10(-6) mol.L-1) significantly increased lactate dehydrogenase (LDH) release in primary mouse cortical neurons exposed to monosodium glutamate (MSG, 0.1 mmol.L-1), indicating enhanced neurotoxicity.
- Pre-incubation with naloxone (0.1 mmol.L-1) reversed the increased LDH release caused by morphine and MSG co-treatment.
- Morphine potentiated MSG-induced elevation of intracellular free Ca2+ ([Ca2+]i), suggesting calcium overload as a key mechanism in this enhanced excitotoxic neuronal damage.
Impact:
- Provides evidence that morphine exacerbates excitotoxic neuronal injury.
- Highlights the potential of naloxone as an antagonist to mitigate opioid-induced neurotoxicity.
- Suggests that modulating intracellular calcium levels is crucial in understanding and treating excitotoxic neuronal damage.