Effects of Diazepam on Hippocampal Excitability in the Rat: Action in the Dentate Area

Acute and chronic experiments were performed on rats to examine the effects of diazepam (Valium) on recurrent inhibition in the monosynaptic perforant path-dentate synapse of the dentate area of the dorsal hippocampus. Evidence was obtained which indicated that diazepam facilitated a presumably GABA mediated post synaptic recurrent inhibition in both acute and chronic preparations at 1 and 2 mg/kg doses (IP). Acute studies also revealed that diazepam prolonged recurrent inhibition, possibly by lengthening the IPSP. An effect of the drug on cholinergically mediated positive feedback from the septum could not be ruled out, however. Taken together, this study extends the evidence that diazepam acts centrally on GABA mediated inhibition in the limbic system. Furthermore, the limbic action of diazepam revealed here suggests a mechanism for the anticonvulsant properties of diazepam in epilepsy involving subcortical (limbic) circuitry.