Effect of the antimetabolite, 6-aminonicotinamide, on sound-induced seizures in mice

• Published in: Experimental neurology Vol. 14; no. 1; pp. 86 - 98
• Main Authors: Geller, Lester M., Cowen, David, Wolf, Abner
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 1966
• Subjects: Animals; Antimetabolites - pharmacology; Brain Stem - drug effects; Brain Stem - pathology; Mice; Niacinamide - pharmacology; Pentylenetetrazole - toxicity; Seizures; Sound - adverse effects
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/0014-4886(66)90026-4

One-month-old male Swiss-Webster mice, from stock selectively inbred for susceptibility to sound-induced seizures, were injected with a single dose (20, 10, 5 or 1 mg/kg, ip) of 6-aminonicotinamide (6-AN), a potent antimetabolite of nicotinamide. Controls received equivalent volumes of water. Within 4 days after inoculation with 20 or 10 mg/kg, the running attacks and maximal extensor seizures seen in response to a ringing bell before treatment, were abolished in every animal. Testing for 3–4 months, even with increased duration or intensity of the sound stimulus, or both, failed to yield a single recurrence of reactivity. Control animals and those injected with 1 mg/kg of 6-AN displayed typical preinoculation responses throughout the experiment. Abolition of responses in the 5-mg/kg group occurred 3 days after inoculation, but these could be reinstituted on the next day by increasing the sound intensity. Thereafter, the reactions of these animals to the seizure tests were highly variable, in some instances appearing after exposure to only routine levels of sound stimulation and in others fading completely or changing in severity. None of the mice in this experiment displayed any severe, and few, any lasting motor disability as a consequence of their treatment with 6-AN. Limited tests of the animals' responses to auditory stimuli, other than the ringing bell, suggested that those receiving the higher doses of 6-AN, and to a lesser extent also those in the 5-mg group, had suffered a reduction in the appreciation of sound. Histological examination of the central nervous system of mice receiving 20 and 10 mg/kg of 6-AN revealed changes in nuclei of the medulla, pons and midbrain, attributable to this agent, which were not found in the animals receiving 5- and 1-mg/kg doses, or in the controls. In none, however, has there been a clear demonstration, as yet, of lesions in central auditory structures, though a search for these is continuing. The peripheral auditory system has not yet been examined. Insofar as we are aware, 6-AN is the first agent reported to be capable of abolishing audiogenic seizures in highly susceptible animals after a single inoculation of a considerably less than lethal dose.