INFLUENCE OF INTRACEREBROVENTRICULAR ADMINISTRATION OF TETANUS TOXIN ON EXPERIMENTAL SEIZURES AND PROTECTION AFFORDED BY SOME ANTIEPILEPTICDRUGS IN MICE

The dose of the intracerebroventricularly administered (i.c.v.) tetanu s toxin (Tetx) evoking the death of 50% of experimental mice (LD50) wa s estimated to be 18.0 (11.5-28.2) times the minimal lethal dose (MLD) . MLD is defined as the lowest dose of Tetx necessary to kill a 20-g a lbino mouse within 96 h after intraperitoneal treatment. Tetx (0.25 an d 0.5 LD50) increased the convulsive threshold of electric current fro m 24 to 96 and 120 h, respectively, following i.c.v. administration. B oth doses of Tetx diminished convulsant potencies of pentylenetetrazol e, bicuculline, aminophylline and pilocarpine 24 h after application. At the same time Tetx (0.5 LD,,) increased the protection afforded by carbamazepine, valproate, phenobarbital and diazepam in maximal electr oshock (MES) by approximately 36, 11, 21 and 26%, respectively, withou t affecting total blood plasma levels of antiepileptic drugs. No marke d changes in gamma-aminobutyric acid (GABA) concentration and total ac tivity of L-glutamic acid decarboxylase (GAD) assessed in the whole-br ain homogenates resulted from Tetx treatment. Our results seem to indi cate that low doses (< LD50) of i.c.v. administered Tetx may lead to a relative prevalence of inhibitory over excitatory processes in the ce ntral nervous system suggesting a complex action of Tetx at the neuron al level. (C) 1998 The Italian Pharmacological Society.