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Finasteride blocks the reduction in ictal activity produced by exogenous estrous cyclicity
C A Frye1, T J Scalise, L E Bayon
1Department of Psychology, Connecticut College, New London 06320, USA.
Journal of Neuroendocrinology
|June 18, 1998
Summary
Estrus reduces seizure activity and neuronal loss, potentially due to increased 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP). Reduced 3alpha,5alpha-THP may restore seizure threshold.
Area of Science:
- Neuroscience
- Endocrinology
- Pharmacology
Background:
- The neurosteroid 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) plays a role in regulating neuronal excitability.
- Hormonal fluctuations, particularly during the estrous cycle, can influence seizure susceptibility.
Purpose of the Study:
- To investigate the impact of reduced 3alpha,5alpha-THP production on seizure activity.
- To explore the neuroprotective and anti-seizure effects associated with the estrous condition.
Main Methods:
- Ovariectomized rats were used to model diestrus and estrus conditions, with estrus induced by estradiol-17-benzoate (EB) and progesterone.
- A 5alpha-reductase inhibitor, finasteride, was administered to reduce 3alpha,5alpha-THP levels.
- Perforant pathway stimulation was used to induce and measure seizure activity.
- Performance on the Morris water maze and hippocampal neuronal loss were assessed.
Main Results:
- The estrous condition showed fewer and shorter partial seizures, improved cognitive function, and reduced hippocampal neuronal loss compared to other conditions.
- Elevated central and plasma 3alpha,5alpha-THP levels were observed during estrus.
- Finasteride administration in estrous rats negated the protective effects, suggesting a role for 3alpha,5alpha-THP.
Conclusions:
- Estrus exhibits antiseizure properties, partly mediated by the neurosteroid 3alpha,5alpha-THP.
- A decline in 3alpha,5alpha-THP may contribute to increased seizure susceptibility.