Interactions between the Central Nervous System and Hormones 87 



depressed behaviorally that the threshold of EEG and behavioral arousal 

 is elevated even higher than during sleep. 



With the techniques of measuring the two thresholds available for register- 

 ing indices of the functional state of the brain, the effects of sex steroids on 

 these thresholds were assessed and correlated with their known effects on 

 behavior and on pituitary activation. 



EFFECTS OF PROGESTERONE 



Some years ago at Duke University, in work only recently published in 

 detail (42), it was discovered that progesterone in the estrous or estrogen- 

 treated rabbit exerts a diphasic effect on the threshold of pituitary activation. 

 During the first few hours after injection of progesterone (2 mg s.c, in oil) 

 the threshold is lowered, as evidenced by the finding that the ovulatory 

 sequence can be initiated by vaginal stimulation, a method which is practically 

 ineffective in the absence of progesterone. By 24 hr after progesterone 

 treatment, however, the pituitary activation threshold is highly elevated : not 

 only is vaginal stimulation ineffective but so is the coital stimulus itself, 

 provided the rabbit will mate. Behaviorally during this latter period the 

 rabbit is distinctly less estrous whereas during the first few hours after 

 progesterone she seems to be "hotter" than when only estrogen is supplied. 

 Thus there appears to be a diphasic effect of progesterone both on estrous 

 behavior and on pituitary activation, the second or inhibitory phase of 

 which is much better known than the earlier phase of facilitation. 



The curve in Fig. 7 shows the diphasic effect of an injection of progesterone 

 on the EEG arousal threshold and the continued elevation of the threshold 

 following a second injection of the steroid 24 hr after the first (43). This 

 curve is paralleled by the changes in EEG afterreaction threshold tabulated 

 at the bottom. During the period of lowered thresholds, the rabbit attacked 

 another female, mated with a male and revealed EEG afterreactions to 

 coitus and to vaginal stimulation as well as to the electrical stimulation 

 employed to assess the afterreaction threshold. As the threshold rose the 

 rabbit became anestrous and EEG afterreaction became difficult or impossible 

 to achieve even with electrical stimulation of the hypothalamus. 



Figure 8 shows not only the two threshold curves during the first 10 hr 

 after a single injection of progesterone to an ovariectomized estrogen-primed 

 rabbit but also depicts the duration of the phases of the EEG afterreactions. 

 Both thresholds remained depressed from one and one-half to four and 

 one-half hours after the steroid injection. It is apparent that the rabbit, 

 although estrogen-primed, was anestrous prior to, and later than six hours 

 after progesterone treatment, but that during the period of lowered thresholds 

 she mated and revealed the EEG afterreaction to coitus and to vaginal 

 stimulation. During this stage the sleep spindles of the EEG afterreaction 

 started immediately on electrical stimulation and once post-coitally. 



7 



