The Gonad-Brain Relationship: Effects of Female Sex Hormones on Electroshock Convulsions in the Rat

Abstract
The effects of ovariectomy and ovarian hormones on brain excitability were investigated in rats by measuring: (a) minimal electroshock seizure threshold, and (b) maximal electroshock seizure pattern. Increased excitability or greater convulsive reactivity is indicated by a decreased threshold and by alterations in the duration of the tonic and clonic components of a maximal seizure, i.e., shortening of tonic flexion and/or lengthening of tonic extension. These procedures and treatments were studied: (a) ovariectomy, before and after puberty, with or without hormonal replacement therapy; (b) administration of estradiol and progesterone, alone or in combination, in intact, castrated or hypophysectomized male or female rats; and (c) administration of testosterone and methylandrostenediol to compare the central nervous effects of male and female sex steroids. Body and organ weights were measured and compared with the changes in convulsability. The main results were: (a) Ovariectomy. After sexual maturation intact females demonstrated greater convulsability than rats ovariectomized before puberty. This was shown by lower seizure thresholds and shorter tonic flexor phases in intact rats as compared with castrated females. However, when ovariectomy was performed after puberty, difference in convulsability was not observed even 3 weeks after operation. (b) Sex steroids. Administration of estradiol to intact mature males and to ovariectomized immature and mature females markedly lowered seizure thresholds. This excitatory action of estradiol was apparent 2 to 7 days after treatment was started, and continued for the duration of treatment; it occurred at doses from 500 μg to 4 μg/100 g body weight/day and was proportional to the dose administered. Similar effects of estradiol in hypophysectomized rats demonstrated that the convulsant action of the hormone was not mediated through the pituitary trophic hormones. Progesterone (500 μg/100 g body weight/day) rapidly and significantly raised the seizure threshold in female rats but had no immediate effect in males. This anticonVulsant action in females was transient and was replaced after 20 days of treatment by a moderate convulsant effect in both males and females. Testosterone and methylandrostenediol (500 μg/100 g body weight/day) significantly lowered seizure threshold after 9 to 20 days of injections in intact adult male rats; however, this fall in threshold was less marked than that produced by estradiol. Thus estradiol appeared to have a more marked central excitatory action than progesterone, testosterone or methylandrostenediol. In addition, progesterone exhibited both an anti-convulsant and a con vulsant action in female rats. It is concluded that sex steroids are capable of altering thresholds and convulsive patterns in the brain and thus play a basic role in aspects of central nervous system physiology other than those exclusively concerned with sexual functions.