Abstracts

Rationale: Sex differences in epilepsy have been suggested by clinical studies as well as animal models, but are not universal, and some issues are controversial. One reason for variability may be that sex differences are present in the normal EEG. To address that hypothesis, we evaluated the EEG of normal male and female rats, using a common laboratory rat strain, the Sprague-Dawley rat. Methods: Adult male and female Sprague-Dawley rats (Charles River, 2-3 months old) were anesthetized and placed in a stereotaxic apparatus to implant electrodes. A twisted bipolar electrode was implanted in each dorsal hippocampus. Epidural screws were placed over the frontal and occipital cortices bilaterally. After 2 weeks, rats were recorded daily for 16-20 days between 9:00 and 12:00 a.m. to collect >5 min of EEG during periods of exploration, quiet immobility, and sleep. Exploration is defined here as walking; immobility as a stationary posture with eyes open; and sleep as immobility with eyes closed and predominance of delta waves in the cortical EEG. Wideband signals (1-6000 Hz) were amplified 350x and transmitted by a digital telemetry device (Biosignal Group). The signal was amplified 2x, and sampled at 2 kHz/channel (Biopac Systems). All female rats were evaluated daily to ensure that they maintained regular 4-day estrous cycles, based on vaginal cytology. Results: All females (n=5), but no males (n=3), exhibited 7-12 Hz bilateral, synchronous, spike and wave discharges (SWDs). SWDs were observed during periods of quiet immobility and sleep, but not exploration. SWDs were blocked by ethosuximide (ETX, 100 mg/kg i.p., n=3 rats), suggesting that SWDs were similar in mechanism to absence seizures. However, SWDs were easily terminated by auditory stimuli, suggesting differences from classic absence seizures. SWDs did not appear to vary with the estrous cycle, based on a comparison of SWDs that occurred during periods of quiet immobility (duration of SWDs/duration of quiet immobility; range: Metestrus, 81-86%; Diestrus 2, 76-87%; Proestrus, 81-89%; Estrus, 86-88%; n= 8 estrous cycles in 2 rats). Conclusions: Normal young adult female Sprague-Dawley rats exhibit SWDs during quiet immobility and sleep, but these do not appear to occur in males. These data suggest a sexual dimorphism in EEG that may reflect the predisposition of absence epilepsy in females. Taken together with evidence from other studies that SWDs occur in other rat strains, such as Fischer and Long-Evans, the data suggest that the majority of laboratory rat strains have a genetic predisposition for SWDs. Furthermore, SWDs in female rats may explain previous reports which suggest that adult female rats exhibit decreased performance on some behavioral tests relative to males, because SWDs could interfere with memory consolidation during quiet immobility and sleep. Supported by NIH and the Epilepsy Foundation.