Inhibition of DFMO-induced audiogenic seizures by chlordiazepoxide

Mice given 1% alpha-difluoromethylornithine (DFMO) in the drinking water for 5 weeks developed a hyperactive behavior characterized by uncontrolled running upon stimulation with noise. The running was followed by seizures and sometimes death. These behaviors are characteristic of audiogenic seizures. Strain differences in susceptibility to DFMO-induced audiogenic seizures were observed. The order of sensitivity to this DFMO effect was: C3HeB/FEJ=C3H/HeN>CBA/J=BALB/c. Chronic DFMO treatment was found to deplete whole brain putrescine and spermidine, but not spermine nor gamma-aminobutyric acid (GABA), in the 2 strains of mice analyzed, C3H/HeN and BALB/c. The audiogenic seizures were eliminated by pretreatment with the benzodiazepine, chlordiazepoxide (Librium) (40 mg/kg, ip) 105 minutes prior to testing for seizures.