The interaction of chlordiazepoxide and sodium valproate in the nucleus accumbens of the rat

Benzodiazepines are known to facilitate GABA-ergic transmission at synaptic sites, while sodium valproate is an anticonvulsant drug which is reported to elevate GABA levels in the brain. In order to determine whether these two drugs interact functionally at GABA receptor sites, graded doses of chlordiazepoxide (CDZ) and sodium valproate were injected bilaterally into the nucleus accumbens and their effect on the dopamine (DA)-induced stimulation of motor activity was studied. Both of these compounds, as well as GABA, produced an inhibition of the hyperactivity induced by the bilateral injection of DA into the nucleus accumbens. Bicuculline, the GABA receptor antagonist, blocked the effect of CDZ on the DA-induced hyperactivity. A low dose of CDZ (2 μg), which by itself did not significantly inhibit the effect of DA, potentiated the inhibition of the hyperactivity produced by valproate. These results suggest that CDZ and sodium valproate can interact functionally at GABA-ergic sites in the central nervous system.