Benzodiazepines increase tonic component of postdecapitation convulsions in mice

Abstract

The effects of benzodiazepines (BDZs) and GABA system on tonic and clonic component of postdecapitation convulsion (PDC) were studied in mice. Mice decapitated at the occipito-cervical junction, exerted biphasic convulsions, i.e., initially tonic and subsequently clonic convulsions. BDZs such as diazepam or clonazepam increased tonic and clonic components of PDC. These effects were not antagonized by Ro 15-1788, a benzodiazepine receptor antagonist. The increased tonic component was antagonized by the GABA receptor antagonists, bicuculline and picrotoxin, whereas the clonic component was augmented by them. Aminooxyacetic acid, which increases the endogenous GABA content by inhibiting the GABA-transaminase, increased the tonic component significantly; this increase was antagonized by both bicuculline and picrotoxin. Muscinol, a GABA agonist, however did not affect the tonic components but rather augmented the clonic component. Bicuculline and picrotoxin did not antagonize this effect of muscimol. These results indicate that endogenous GABA may play a crucial role in mediating the tonic component of PDC and the facilitation of this component by BDZs may also be due to the activation of GABA in the spinal cord. Furthermore, the mechanisms of the tonic component may be different from that of the clonic component.