Valproate enhances GABA-A mediated inhibition of locus coeruleus neurones in vitro

It has previously been claimed that the anticonvulsant valproate acts by augmenting GABA-ergic transmission, however, the data supporting this claim is controversial. Here we demonstrate that valproate strongly and reversibly potentiates the depressant effects of the GABA-A receptor agonist muscimol...

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Bibliographic Details
Published in:Naunyn-Schmiedeberg's archives of pharmacology 1988-12, Vol.338 (6), p.655-657
Main Authors: OLPE, H.-R, STEINMANN, M. W, POZZA, M. F, BRUGGER, F, SCHMUTZ, M
Format: Article
Language:English
Subjects:
Animals
Anticonvulsants. Antiepileptics. Antiparkinson agents
Biological and medical sciences
gamma-Aminobutyric Acid - physiology
In Vitro Techniques
Locus Coeruleus - cytology
Locus Coeruleus - drug effects
Male
Medical sciences
Muscimol - pharmacology
Neurons - drug effects
Neuropharmacology
Pharmacology. Drug treatments
Rats
Rats, Inbred Strains
Receptors, GABA-A - metabolism
Valproic Acid - pharmacology
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Summary:It has previously been claimed that the anticonvulsant valproate acts by augmenting GABA-ergic transmission, however, the data supporting this claim is controversial. Here we demonstrate that valproate strongly and reversibly potentiates the depressant effects of the GABA-A receptor agonist muscimol on locus coeruleus neurones recorded extracellularly from a midpontine slice preparation of the rat. The depressant effect of muscimol (2 microM) is augmented by bath applied valproate at concentrations of 50 microM, 100 microM and 1 mM. The effect of GABA is also potentiated by valproate. The potentiating effect is selective since the cell inhibition elicited by the GABA-B receptor agonist baclofen is not affected. Valproate on its own had no effect on the firing frequency.
ISSN:0028-1298
1432-1912
DOI:10.1007/BF00165630