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 of N-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, alpha-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.


CONCLUSIONS
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.
Manto
M
M
Laboratoire de Neurologie Expérimentale, ULB-Erasme, Bruxelles, Belgium. mmanto@ulb.ac.be
Laute
M-A
MA
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D020329:Essential Tremor / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism; D005990:Glycerol / Q000032:analysis / Q000378:metabolism; D006246:Harmaline / Q000494:pharmacology; D019344:Lactic Acid / Q000032:analysis / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D016202:N-Methylaspartate / Q000378:metabolism; D019289:Pyruvic Acid / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D019344:Lactic Acid; D000431:Ethanol; D018698:Glutamic Acid; D016202:N-Methylaspartate; D019289:Pyruvic Acid; D006246:Harmaline; D005990:Glycerol