A possible mechanism for the beneficial effect of ethanol in essential tremor
Copyright policy )A possible mechanism for the beneficial effect of ethanol in essential tremor
Background: Essential tremor is one of the most common movement disorders in elderly people. The hypothesis of a disregulation ofN‐methyl‐d‐aspartate (NMDA) pathways has been suggested. It was shown experimentally that infusion of NMDA in cerebellar nuclei down‐regulates glutamate release.Methods: We assessed the effects of intranuclear administration of harmaline on the NMDA‐mediated regulation of glutamate in rats using reverse dialysis. We hypothesized that ethanol, which improves essential tremor in the clinic, antagonizes the effect of harmaline upon glutamatergic transmission. We tested the interaction of ethanol and harmaline upon glycerol (a marker of membrane turn‐over), lactate, and pyruvate concentrations.Results: Harmaline increased the concentrations of glutamate and impaired the NMDA‐mediated regulation of glutamate. Ethanol decreased the concentrations of glutamate during NMDA stimulation in case of pre‐administration with harmaline. Concentrations of glycerol rose with harmaline. Glycerol levels markedly decreased during NMDA infusion when inhibitors of nitric oxide synthase, α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate antagonists or NMDA antagonists were administered. Harmaline increased lactate/pyruvate ratios during NMDA infusion but these ratios returned to normal values in presence of ethanol.Discussion: We provide a possible mechanism for the beneficial effect of ethanol on essential tremor. The concept of glutamatergic disregulation underlying essential tremor is highlighted. Consequences for our understanding of essential tremor are discussed.
- Université Libre de Bruxelles Belgium
Glycerol, Male, Lactic Acid -- metabolism, N-Methylaspartate, Essential Tremor, Microdialysis, Central Nervous System Depressants -- pharmacology, Wistar, Glutamic Acid, Essential Tremor -- metabolism, Harmaline, Brain -- drug effects, Glycerol -- metabolism, Pyruvic Acid, Brain -- metabolism, Lactic Acid -- analysis, Glycerol -- analysis, Animals, Lactic Acid, Rats, Wistar, Central Nervous System Stimulants -- pharmacology, Pyruvic Acid -- metabolism, Ethanol, Glutamic Acid -- drug effects, Glutamic Acid -- metabolism, Brain, Central Nervous System Depressants, Sciences bio-médicales et agricoles, Harmaline -- pharmacology, Rats, N-Methylaspartate -- metabolism, Central Nervous System Stimulants, Ethanol -- pharmacology, Pyruvic Acid -- analysis
Glycerol, Male, Lactic Acid -- metabolism, N-Methylaspartate, Essential Tremor, Microdialysis, Central Nervous System Depressants -- pharmacology, Wistar, Glutamic Acid, Essential Tremor -- metabolism, Harmaline, Brain -- drug effects, Glycerol -- metabolism, Pyruvic Acid, Brain -- metabolism, Lactic Acid -- analysis, Glycerol -- analysis, Animals, Lactic Acid, Rats, Wistar, Central Nervous System Stimulants -- pharmacology, Pyruvic Acid -- metabolism, Ethanol, Glutamic Acid -- drug effects, Glutamic Acid -- metabolism, Brain, Central Nervous System Depressants, Sciences bio-médicales et agricoles, Harmaline -- pharmacology, Rats, N-Methylaspartate -- metabolism, Central Nervous System Stimulants, Ethanol -- pharmacology, Pyruvic Acid -- analysis
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