Inhibition of pentylenetetrazol induced genetically-determined stereotypic convulsions in tottering mutant mice by diazepam.

Genetically-determined stereotypic behavioral convulsions (GDSC) resulting from the autosomal recessive mutation tottering (tg) were studied in C57BL/6J mice. GDSC was found to be reliably induced in (tg/tg) homozygotes with 30 mg/kg pentylenetetrazol (PTZ), a dose that is significantly below the threshold for induction of generalized clonic convulsions in (tg/+) heterozygotes and (+/+) wild type C57BL/6J mice. The effects of anticonvulsant drugs on GDSC were studied in (tg/tg) mice induced by 30 mg/kg PTZ. Ethosuximide (250 mg/kg), phenytoin (25 and 50 mg/kg), sodium phenobarbital (25 and 50 mg/kg), naloxone (6 mg/kg), valproic acid (150 mg/kg), sodium valproate (200 mg/kg) and aminooxyacetic acid (25 mg/kg) were all without effect on PTZ induced GDSC. In contrast to its usual anticonvulsant action, phenytoin caused GDSC in (tg/tg) mice. Diazepam (4 mg/kg) was completely effective in blocking GDSC 2 hr post administration. Ethosuximide (250 mg/kg), which did not protect (tg/tg) mice against GDSC, was able to protect both (tg/tg) and (tg/+) mice against generalized clonic-tonic convulsions induced by 85 mg/kg PTZ. These results suggest a novel mechanism of action for the induction of GDSC by 30 mg/kg PTZ in (tg/tg) mice which may involve benzodiazepine receptors.