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A Rat Model of Epilepsy in Women: A Tool to Study Physiological Interactions between Endocrine Systems and Seizures

The Nathan Kline Institute for Psychiatric Research (H.E.S., D.F., P.P.), Center for Dementia Research, Orangeburg, New York 10962; Departments of Child and Adolescent Psychiatry, Physiology, and Neuroscience (H.E.S., P.P.), New York University Langone Medical Center, New York, New York 10021; Department of Neurosurgery (G.H.M.-P.), University of Pennsylvania, Philadelphia, Pennsylvania 19104; Department of Psychology and Program in Developmental Neuroscience (D.P.M.), College of Staten Island-City University of New York, Staten Island, New York 10314; Miller School of Medicine (C.L.H.), University of Miami, Miami, Florida 33136; and Department of Biomedical Sciences (N.J.M.), University of Guelph, Guelph, Ontario, Canada N1G 2W1

Address all correspondence and requests for reprints to: Helen E. Scharfman, Ph.D., The Nathan Kline Institute, 140 Old Orangeburg Road, Building 35, Orangeburg, New York 10962. E-mail: hscharfman{at}nki.rfmh.org.

Epilepsy in women is influenced by endocrine status and antiepileptic drugs, but without an animal model, the effects of endocrine variables and antiepileptic drugs cannot be easily dissociated from the influence of epilepsy itself. Animal models have had limited utility because experimentally induced seizures typically result in reproductive failure. This study was conducted to develop an improved animal model. The muscarinic convulsant pilocarpine was used to elicit status epilepticus (SE) in adult female Sprague Dawley rats. The selective estrogen receptor modulator raloxifene was administered 30 min before pilocarpine. An anticonvulsant barbiturate, pentobarbital, was injected 5–10 min after the onset of SE and at least once thereafter to minimize acute convulsions. Mortality, morbidity, estrous cyclicity, and the ultimate success of the procedure (i.e. induction of recurrent, spontaneous seizures) were monitored. The combination of raloxifene and pentobarbital led to significantly improved estrous cyclicity compared with previous methods. Animals treated with raloxifene and pentobarbital became epileptic, as defined by the recurrence of spontaneous convulsions in the weeks after SE. The results of this study provide an improved animal model to examine the interactions between seizures and ovarian hormone secretion. The results also suggest that treatment of SE with raloxifene may benefit women with SE.