Sex Difference in Susceptibility to Epileptic Seizures in Rats: Importance of Estrous Cycle

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Abstract
Sex difference in seizure susceptibility is one of the unresolved issues of epilepsy. It is known that estrogen is excitatory and progesterone is inhibitory to the central nervous system. Therefore, it is to be expected that seizure susceptibility may be associated with the estrous cycle, which should be tested in epilepsy research. Otherwise, different results in epilepsy studies could be an artifact of the estrous cycle. Reports in the literature are inconsistent about testosterone effects on seizures. In light of these considerations, sex differences in seizure susceptibility were restudied in rats. There was no significant sex difference in mean latencies to picrotoxin-induced seizures; prestrous-females had the shortest latencies to epileptic seizures compared to males and estrousfemales. With testosterone-injected rats, there was either no sex difference in latencies (to akinetic and focal seizures) or females had significantly shorter latencies than males (to status epilepticus, generalized tonic-clonic seizures, and myoclonic seizures). Testosterone-treated male rats had a significantly longer mean latency than controls for status epilepticus only; otherwise, these males showed no significant differences between mean latencies before and after testosterone (to focal, myoclonic, or generalized tonic-clonic seizures). In females, mean latencies to myoclonic seizures and status epilepticus were significantly shorter after testosterone than before. It was concluded that there is a sex difference in susceptibility to epileptic seizures in rats, provided that the estrous cycle is taken into account. Testosterone may increase and decrease seizure susceptibility in females and males, respectively. These effects may be important for understanding the mechanisms of epileptic phenomena and may provide some important clues to epilepsy treatment.