Influence of intracerebroventricular administration of tetanus toxin on experimental seizures and protection afforded by some antiepileptic drugs in mice.

The dose to the intracerebroventricularly administered (i.c.v.) tetanus toxin (Tetx) evoking the death of 50% of experimental mice (LD50) was estimated to be 18.0 (11.5-28.2) times the minimal lethal dose (MLD). MLD is defined as the lowest does of Tetx necessary to kill a 20-g albino mouse within 96 h after intraperitoneal treatment. Tetx (0.25 and 0.5 LD50) increased the convulsive threshold of electric current from 24 to 96 and 120 h, respectively, following i.c.v. administration. Both doses of Tetx diminished convulsant potencies of pentylenetetrazole, bicuculline, aminophylline and pilocarpine 24 h after application. At the same time Tetx (0.5 LD50) increased the protection afforded by carbamazepine, valproate, phenobarbital and diazepam in maximal electroshock (MES) by approximately 36, 11, 21 and 26%, respectively, without affecting total blood plasma levels of antiepileptic drugs. No marked changes in gamma-aminobutyric acid (GABA) concentration and total activity of L-glutamic acid decarboxylase (GAD) assessed in the whole-brain homogenates resulted from Tetx treatment. Our results seem to indicate that low doses (< LD50) of i.c.v. administered Tetx may lead to a relative prevalence of inhibitory over excitatory processes in the central nervous system suggesting a complex action of Tetx at the neuronal level.