Caffeine blocks absence seizures in the tottering mutant mouse

The neurological tottering mutant mouse is characterized by frequent "absence" seizures accompanied by bilateral synchronous spike and wave EEG bursts. Under anesthesia, adult homozygous tottering mice were implanted with permanent epidural electrodes, and at least 7 days elapsed before electrocorticograms in unrestrained mice were scored for seizure incidence and duration. Caffeine (5, 10, 15 mg/kg, n = 8) injected intraperitoneally (i.p.) at the fourth hour of 8-h recording sessions significantly (p less than 0.001 for 10 and 15 mg) decreased seizure incidence as compared with control saline injections. Spike and wave bursts were eliminated during the 30 min after injection and reached 50% preinjection levels between the first and the second hour after injection. Another central nervous system (CNS) stimulating drug, amphetamine (1 mg/kg; n = 5), under identical conditions failed to decrease seizure incidence in this mutant.