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 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.
Olpe
H R
HR
Pharmaceuticals Division, Ciba-Geigy Ltd., Basel, Switzerland.
Steinmann
M W
MW
Pozza
M F
MF
Brugger
F
F
Schmutz
M
M
D000818:Animals; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000166:cytology / Q000187:drug effects*; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D014635:Valproic Acid / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid