Further studies on the site of action of diazepam: Anticonvulsant effect in the rabbit

Abstract

The site of the anticonvulsant action of diazepam was studied by means of direct intracerebral chemostimulation in conscious rabbits with chronically implanted cannulae and recording electrodes. In order to evaluate anticonvulsant effectiveness, two procedures were used: (a) elevation in pentylenetetrazol (PTZ) threshold for appearance of spike activity in the EEG record; (b) elevation in the threshold of limbic after-discharges. Diazepam was injected in one of three regions: anterior amygdaloid nucleus (AA), basal amygdaloid nucleus (AB), and dorsal hippocampus (DH). Application of diazepam in the AA strongly elevated the PTZ threshold in a reversible and doserelated manner; injections in the AB or DH were ineffective. Phenobarbital was also ineffective in all regions investigated. The threshold of amygdalo-hippocampal after-discharges was elevated after application of diazepam in the AA, but not after injection in the DH. Hippocampal-amygdaloid after-discharges were not influenced by the drug from either the AA or DH. It is concluded that the amygdaloid nucleus, and particularly its anterior part, plays a crucial role in the anticonvulsant effect of diazepam in the rabbit.