Circadian rhythms and seizure susceptibility: Relation to 5-hydroxytryptamine and norepinephrine in brain

Abstract

Susceptibility to audiogenic seizures was determined in DBA/2J mice which were tested at 2-day intervals between 12 and 42 days of age; individual animals were tested only once; the seizure tests were conducted either during the day or at night. Differences in seizure susceptibility were found as a function of age and as a function of time-of-testing. Maximum day-night differences in seizure susceptibility were observed in 26-day-old animals, and all subsequent experiments were conducted in mice of this age. Susceptibility to sound- and electrically-induced seizures were studied in DBA/2J, C57BL/6J and F 1 hybrid mice tested at 10 different times of the day-night cycle; individual animals were tested only once. Statistically significant differences in susceptibility to sound and electrically-induced seizures as a function of time-of-testing were observed in DBA/2J and F 1 hybrid mice; C57BL/6J mice also exhibited some periodicity in seizure susceptibility although this was only marginally significant. Levels of 5-hydroxytryptamine (serotonin, 5-HT) and norepinephrine (NE) were determined in cortical, diencephalic and brain stem samples from brains of DBA/2J, C57BL/6J and F 1 hybrid mice; samples were assayed either at noon or at midnight. No differences in levels of NE were observed in any of the tissues taken either at noon or at midnight. Statistically significant differences in levels of 5-HT were observed in all parts of brain between samples obtained at noon and at midnight; levels of 5-HT were between 10 and 20 per cent lower at midnight than at noon. No significant strain differences in levels of 5-HT and NE were observed. The correlation between seizure susceptibility and levels of these biogenic amines is discussed.