Abstracts

RATIONALE: Isolation housing has been reported to act differentially as a stressor in female and male lab animals. As responses or adaptations to stress have been shown to influence brain excitability, we wanted to determine if mild chronic stress or brief, acute stress would differentially affect seizure induction. Therefore the objective of this study was to determine whether different stressors (chronic mild or acute) exerted sex-selective actions on seizure induction in male and female rats.
METHODS: The effect of stress was measured by seizure threshold (ST) determinations, a sensitive measure of seizure susceptibility. The chemoconvulsants, bicuculline (BIC), 0.05mg/ml, or pentylentetrazol (PTZ), 5mg/ml, were slowly infused via a lateral tail vein and ST were determined by recording the time to first twitch/ body weight of the animal. Initially, we assayed the effects of a mild, chronic stressor (10 days of individual versus group housing) on ST. We compared the anticonvulsant effect of diazepam (5 mg/kg) or ethanol (2.5 g/kg) on ST under these different chronic stress conditions. We also studied the effect of an additional brief restraint stress on ST of male and female rats under the two housing conditions.
RESULTS: We found that individual housing reduced BIC ST by approximately 10% in both male and female rats. In contrast PTZ ST were similar between individual and group housed male and female rats. The anticonvulsant effectiveness of diazepam and ethanol were not altered by individual housing in either male and female rats. However, female rats displayed a greater response than male rats to both diazepam and ethanol. For example, ip administration of ethanol increased PTZ seizure thresholds in individually housed animals from 30.8 [plusminus] 0.9 to 46.4 [plusminus] 2.3 mg/kg PTZ in male rats and from 31.3 [plusminus] 2.2 to 54.5 [plusminus] 3.1 mg/kg PTZ in female rats. Acute administration of ethanol also increased BIC ST by 13 or 19% in female rats but only 8 or 9% in male rats (for group or individually housed animals, respectively). The addition of a brief, acute restraint stress decreased ST from 0.203 [plusminus] 0.012 to 0.183 [plusminus] 0.013 mg/kg BIC in individually housed male rats, without altering ST in group housed male rats. Conversely, ST were reduced from 0.292 [plusminus] 0.012 to 0.254 [plusminus] 0.009 mg/kg BIC in group housed female rats, with no effect on individually housed female rats.
CONCLUSIONS: These data showed that both a chronic, mild stress as well as acute stress can influence seizure susceptibility in a laboratory animal model. Furthermore, there were interesting sex differences in responses to stressors as well as anticonvulsants. These data suggest that certain types of stressors, classified as social (modeled by housing conditions) or non-social (modeled by acute restraint stress) may differentially impact the risk for induction of seizures in men and women with epilepsy.
[Supported by: PHS AA11877.]