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

Summary It has previously been claimed that the anti-convulsant 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 M) is augmented by bath applied valproate at concentrations of 50 M, 100 M 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.Send of print requests to H.-R. Olpe at the above address