Alcohol and Ganaxolone Suppress Tremor via Extra-Synaptic GABA
alcohol
cerebellum
harmaline
receptor
tremor
Journal
Tremor and other hyperkinetic movements (New York, N.Y.)
ISSN: 2160-8288
Titre abrégé: Tremor Other Hyperkinet Mov (N Y)
Pays: England
ID NLM: 101569493
Informations de publication
Date de publication:
2023
2023
Historique:
received:
23
02
2023
accepted:
06
05
2023
medline:
24
5
2023
pubmed:
22
5
2023
entrez:
22
5
2023
Statut:
epublish
Résumé
A long-standing question is why essential tremor often responds to non-intoxicating amounts of alcohol. Blood flow imaging and high-density electroencephalography have indicated that alcohol acts on tremor within the cerebellum. As extra-synaptic δ-subunit-containing GABA We tested the hypotheses that low-dose alcohol will suppress harmaline-induced tremor in wild-type mice, but not in littermates lacking GABA Ethanol, 0.500 and 0.575 g/kg, and ganaxolone, 7 and 10 mg/kg, doses that do not impair performance in a sensitive psychomotor task, reduced harmaline tremor compared to vehicle-treated controls in wild-type mice but failed to suppress tremor in littermates lacking the δ or the α6 GABA As cerebellar granule cells are the predominant brain site intensely expressing GABA How does alcohol temporarily ameliorate essential tremor? This study with a mouse model found that two specific kinds of GABA receptor subunits were needed for alcohol to work. As receptors with both these subunits are found mainly in cerebellum, this work suggests this is where alcohol acts to suppress tremor.
Sections du résumé
Background
A long-standing question is why essential tremor often responds to non-intoxicating amounts of alcohol. Blood flow imaging and high-density electroencephalography have indicated that alcohol acts on tremor within the cerebellum. As extra-synaptic δ-subunit-containing GABA
Methods
We tested the hypotheses that low-dose alcohol will suppress harmaline-induced tremor in wild-type mice, but not in littermates lacking GABA
Results
Ethanol, 0.500 and 0.575 g/kg, and ganaxolone, 7 and 10 mg/kg, doses that do not impair performance in a sensitive psychomotor task, reduced harmaline tremor compared to vehicle-treated controls in wild-type mice but failed to suppress tremor in littermates lacking the δ or the α6 GABA
Discussion
As cerebellar granule cells are the predominant brain site intensely expressing GABA
Highlights
How does alcohol temporarily ameliorate essential tremor? This study with a mouse model found that two specific kinds of GABA receptor subunits were needed for alcohol to work. As receptors with both these subunits are found mainly in cerebellum, this work suggests this is where alcohol acts to suppress tremor.
Identifiants
pubmed: 37214542
doi: 10.5334/tohm.760
pmc: PMC10198231
doi:
Substances chimiques
Ethanol
3K9958V90M
gamma-Aminobutyric Acid
56-12-2
ganaxolone
98WI44OHIQ
Harmaline
CN58I4TOET
Receptors, GABA-A
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
18Informations de copyright
Copyright: © 2023 The Author(s).
Déclaration de conflit d'intérêts
The author has no competing interests to declare.
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