REM sleep deprivation facilitates the estrogen effect on heterotypical sexual behavior in male rats

Gonadectomized male rats were submitted to REM sleep deprivation (REMd) for 120 hr and their hetero and homotypical sexual response to estradiol benzoate (EB) was tested. Subjects (Ss) receiving 20 micrograms EB showed lordosis quotients (LQ) twice as high as those receiving 10 micrograms EB and at the same time the LQs in these groups were higher than in the non-REMd groups. Gonadectomized-adrenalectomized control Ss showed the highest levels of lordosis throughout the experiment. REMd by itself does not produce lordosis response. The results indicate that the brain structures underlying this behavior in males are probably similar to those in females, since REMd increases lordosis in both cases. The lack of homotypical sexual behavior normally observed in gonadectomized male rats does not seem to be affected by this treatment. The issue of adequate controls for REMd experiments is discussed.     

Cholecystokinin stimulates and inhibits lordosis behavior in female rats

Recently, IP CCK-8 has been shown to inhibit lordosis in sexually experienced, estradiol benzoate (EB) and progesterone (P) primed rats. However, receptivity is influenced by prior sexual experience and/or exposure to sex steroids, as well as the steroid dosage administered before testing. Thus, we examined the effect of CCK-8 (3 micrograms/kg; IP) on lordosis in rats with different degrees of receptivity. Three weeks after ovariectomy, females were treated with EB followed 48 hr later with P, or with EB alone. CCK-8 significantly facilitated lordosis in rats given 5 micrograms EB. Following a 5 week nonexperimental period, animals were more receptive and CCK-8 significantly inhibited lordosis in the 5 or 10 micrograms EB groups. In a separate experiment, rats were ovariectomized, adrenalectomized, and treated with EB alone. As in the first experiment, CCK-8 facilitated and inhibited lordosis. CCK-8's effects were highly dependent on the female's receptivity, facilitating lordosis when receptivity was low and inhibiting lordosis when receptivity was high (but not maximal). In conclusion, IP CCK-8 modulates lordosis behavior independent of P, but its effects depend on the female's degree of receptivity.     

Hormonal control of the perception of the olfactory signals which facilitate lordosis behavior in the male rat

This study was designed to evaluate in the male rat the hormonal requirements for the facilitation of feminine behavior by the odor of male urine. Wistar rats from the WI and WII strains in our colony were orchidectomized (ORCH) as adults. A first group was given a single dose of 75 micrograms estradiol benzoate (EB) and tested for lordosis behavior 48 hr later. Exposure to the odor of male urine by 9 +/- 1 hr before the behavioral session did not increase the number of animals showing lordosis behavior as compared to non exposed controls. A second group of WI rats was given 0.5 micrograms EB every day for 4 to 8 days. A similar number of animals displayed lordosis behavior irrespective of whether they were exposed to the odor of urine before testing. A third group of WI rats was injected with 75 micrograms EB and 1 mg progesterone (P) 39 hr apart. Exposure to the odor of urine during estrogen treatment remained ineffective but significantly increased the number of animals showing lordosis behavior when performed at the time of P injection. A last group of WII rats was given 25 micrograms EB and 100 micrograms or 150 micrograms P 39 hr apart. Although uncapable as such to facilitate lordosis behavior the dose of 100 micrograms P rendered the animals responsive to the odor of urine. It was concluded that (1) the perception by feminized males of olfactory signals from the male was dependent on P; (2) an interaction between hormonal and sensory mechanisms was involved in the facilitation of lordosis behavior in the male rat.     

Lordosis inhibiting effects of endogenous progesterone in the male rat primed with estrogen

The aim of this study was to investigate the mechanisms involved in the inhibitory action of progesterone on estrogen-induced facilitatory effects of estradiol benzoate on lordosis behavior in the male rat. Intact adult male rats were given 1) 25 micrograms estradiol benzoate (EB) and 100 micrograms progesterone (P) at an interval of 42 hr. EB injected animals served as controls 2) EB followed by 3 doses of 400 micrograms dexamethasone (DEXA) and P as above. EB + DEXA injected animals served as controls. Testing for lordosis behavior was performed by 50 +/- hr after EB injection. A significant decrease in the number of the males displaying lordosis in response to the mounts of stimulus males resulted from P injection following EB treatment as compared to EB controls. DEXA treatment significantly reduced the number of EB animals showing lordosis responses but completely prevented the inhibitory effects of exogenous P to occur. Blood P values appeared to be significantly lower in EB + DEXA males than in their EB counterparts. The results provide evidence that endogenous P is involved in the display of lordosis behavior by EB-treated intact males. They mainly suggest that the effects of exogenous P on estrogen-induced lordosis behavior in the intact male rat result from sequential inhibitory mechanisms involving exposure of the animals to the successive action of endogenous and exogenous P.     

Estradiol benzoate facilitates lordosis and ear wiggling of 4- to 6-day-old rats

The effects of exogenous and endogenous steroids on components of female sexual behavior of neonatal male and female rats were investigated. In Experiment 1, 4-day-old rats were treated with 0, 0.1, 1.0, 10, or 100 micrograms/10 g body weight estradiol benzoate (EB) and were tested 44 hr later. In Experiment 2, male rats castrated within 24 to 48 hr of birth were compared with sham operated controls and castrates given steroid replacement. The results indicated that most 6-day-old pups will display lordosis and ear wiggling; therefore, the display of these responses is not dependent upon exogenous steroids. However, a fine-grained behavioral analysis revealed that EB treatment increased the frequency, duration, and intensity of lordosis and the frequency of ear wiggling in infant females, and it increased lordosis duration in males. Castration of infant males decreased the likelihood that male infants would display lordosis, whereas testosterone replacement restored behavior to control levels. These data question the concept that organizational and activational actions of estrogens occur during completely separable times in development and should provide new insights into the development of estrogen receptor function and the process of sexual differentiation of brain and behavior.     

Intrahypothalamic implants of noradrenergic antagonists disrupt lordosis behavior in female rats

There is considerable experimental evidence that hormonal activation of lordosis in female rats involves norepinephrine (NE) neurotransmission. However, no clear picture has emerged regarding either: 1) the neural sites at which NE influences lordosis, or 2) the NE receptor subtype(s) mediating NE effects on lordosis. To address these two issues, the behavioral effects of antagonists with relative specificity for alpha 1, alpha 2, or beta adrenergic receptors were examined. Drugs were administered via bilateral crystalline implants directly into the ventromedial nucleus of the hypothalamus (VMN) or medial preoptic area (MPOA) of ovariectomized female rats primed for 48 hr with 3 micrograms of estradiol benzoate (EB) and given 200 micrograms of progesterone (P) 3.5-4 hr before testing. When applied to the VMN 1 hr before the P injection, the alpha 1 receptor antagonist prazosin reduced lordosis behavior in 86% of animals but in only 10% of rats when applied to the MPOA. However, prazosin did not inhibit lordosis when implanted into the VMN just prior to EB administration. Yohimbine, an alpha 2 receptor antagonist with low affinity for alpha 1 receptors, also suppressed lordosis in 41% of animals with VMN implants and in 37% of rats with MPOA implants. By contrast, the alpha 2 antagonist idazoxan, which has little activity at alpha 1 receptors, did not significantly affect estrous responding when implanted into either the VMN or MPOA. VMN implants of the beta receptor antagonists propranolol and pindolol reduced lordosis behavior in 50% and 86% of rats, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of mesencephalic tegmentum in regulating female rat sexual behaviors

Feminine sexual behaviors were tested in estradiol benzoate (EB) and progesterone (P) primed ovariectomized rats following four types of radiofrequency lesions in the midbrain tegmentum. The dorsomedial lesion (DML) which destroyed the ventromedial central gray including the dorsal raphe nucleus and adjacent area induced high sexual receptivity in the females primed with low dose (0.5 micrograms) of EB-P. All females with DML exhibited lordosis and ear wiggling, the mean lordosis quotient (LQ) being significantly higher than that of castrated controls or sham operated rats. Sexual receptivity in females with ventromedial tegmental lesion was not significantly different from those of the control and sham groups. In contrast to the medially lesioned groups, the mean LQ was low in the animals with bilateral lateral tegmental lesions even when the dose of EB was increased to 2 micrograms which was sufficient to induce high sexual receptivity in castrated and sham operated control females. In the animals with dorsolateral tegmental lesions (DLL), a much more severe loss of lordosis was seen than in those with ventrolateral tegmental lesions (VLL). None of the DLL females displayed sexual behavior throughout the present experiments. These results lead us to conclude that the midbrain dorsomedial tegmental area (ventral central gray and the adjacent area) is concerned with female sexual behavior inhibiting system, whereas the lateral tegmental area may be involved in the facilitatory system.     

Effects of ventromedial nucleus lesions on the display of lordosis behavior in the male rat. Interactions with facilitory effects of male urine

Previous observations showed that exposure to the odor of male urine prior to mating could enhance the display of lordosis behavior in male rats feminized with ovarian hormones. This study was performed to determine in feminized male rats whether the control of lordosis behavior by the olfactory system was mediated by the ventromedial nucleus (VMN) of the hypothalamus. Male rats were orchidectomized (ORCH) as adults and primed with 25 micrograms estradiol benzoate (EB) and 150 micrograms progesterone (P) 40 hr apart. Lordosis behavior was tested 9 +/- 1 hr after P injection. VMN lesions were shown to completely suppress the display of lordosis behavior as compared to sham VMN operated and dorsomedial nucleus (DMN) lesioned animals. Exposure of feminized rats to the odor of male urine by 9 +/- 1 hr before mating significantly increased the proportion of ORCH rats that displayed lordosis behavior in response to male mounts. This effect was abolished by VMN lesions but was maintained in the sham VMN operated and DMN lesioned animals. These results were discussed in the light of the present knowledge on the neuroendocrine and olfactory structures which mediate lordosis behavior in the male rat.     

Light-dark differences in behavioral sensitivity to oxytocin.

Ovariectomized female rats treated with estradiol benzoate (EB) and progesterone (P) were infused intracerebroventricularly with a low (200 ng) or high (1 microgram) dose of oxytocin (OT). The low dose of OT facilitated lordosis behavior only during the dark phase of the light-dark cycle in females that were pretreated with low doses of EB (2 micrograms) and P (250 micrograms). In contrast, the high dose of OT facilitated lordosis behavior during both the light and the dark phases but only in long-term ovariectomized females that were primed with large amounts of EB (2 x 10 micrograms) and P (500 micrograms). In females that were primed with lower amounts of ovarian steroids, the high dose of OT failed to increase levels of lordosis responding in either the dark or light phase. Thus, when female rats are treated with physiological amounts of ovarian hormones and OT, they are more sensitive to the facilitative effects of the OT on lordosis behavior during the dark phase.     

Facilitation of progesterone induced lordosis behavior by phosphodiesterase inhibitors in estrogen primed rats

The effect of 1-methyl,3-isobutylxanthine (MIX) and theophylline (TPH), two phosphodiesterase inhibitors, on the behavioral response induced by low doses of progesterone (P) was studied in ovariectomized estrogen primed Wistar rats. Administration of 50, 100 or 200 μg of P 44 hr after 2 μg of estradiol benzoate (EB) induced lordosis in 25%, 69% and 71% respectively of the rats used. Maximal mean lordosis quotients (LQ) obtained in the control groups were as follows: (50 μg P=7; 100 μg P=32; 200 μg P=41). Maximal mean LQ's were seen in control groups 4 hr after P. Lordosis behavior disappeared in nearly all control rats within 36 hr of P injection. Repeated injections of 4 mg MIX or 10 mg TPH (40 and 44 hr after EB and thereafter every 8 hr up to 96 hr) significantly enhanced and prolonged the response to P. Maximal mean LQ's of experimental groups were as follows: 50 μg P + MIX=45; 50 μg P + TPH=37; 100 μg P + MIX=46; 100 μg P + TPH=68; 200 μg P + MIX=91; 200 μg P + TPH=93. Lordosis was still displayed by more than 50% of the rats treated with MIX or TPH 36 hr after P. Neither MIX nor TPH alone elicited significant lordosis behavior when given to estrogen primed rats. The results suggest that the induction of lordosis behavior by P is mediated through a rise in cyclic nucleotide levels in neurons related to the expression of sexual behavior.     

Hypothalamic nuclear estrogen receptors and lordosis behavior in hamsters

These experiments examined the effects of a high and a low dose of estradiol benzoate (EB) in enhancing lordosis behavior and correlated these effects with the retention of hypothalamic nuclear estrogen receptors (NER) in female hamsters. Ten micrograms EB was significantly more effective in facilitating sexual receptivity in hamsters when it was followed 36 or 48 hr later by 0.5 mg progesterone (P), but not when P was given 24 hr after EB. Low levels of behavioral responses were observed in animals that received P at 24, 36 or 48 hr after 2 micrograms EB. Correspondingly, although the hypothalamic NER levels were equally elevated 24 hr after either a low or a high dose of EB, these receptor concentrations remained high at 36 and 48 hr post EB, only in those animals that received the high estrogen dose. The results of these experiments suggest that the long-term retention of NERs (which is maintained by a single high EB dose) may play an important role in the enhancement of sexual receptivity in hamsters.     

Effects of potassium chloride on sexual behavior and the cortical EEG in the ovariectomized rat

The facilitation of lordosis behavior by the cortical application of KCl has been confirmed. Ovariectomized female rats were injected with estradiol benzoate (EB) for 3 days and then a 15% KCl solution was put into permanent cannulae resting on the cortical dura. Sexual behavior tests were performed 15, 30, 60 and 90 min and 24 hr after KCl application and a lordosis quotient (LQ) was obtained from each 10-mount test. There was a significant increase in the LQ 15 min after KCl application to levels which approached those seen after priming with both EB and progesterone. Although lordosis behavior was facilitated, no EEG changes were found following KCl application in 7 of 9 rats, but there was marked depression of the amplitude of the cortical EEG in the remaining 2. It is concluded that KCl application, a treatment which produces functional decortication by inducing spreading depression, suppresses a cortical inhibitory system for lordosis behavior.     

The effect of hysterectomy on hormone-induced lordosis behavior in hamsters

Ovariectomized-hysterectomized (OH) and ovariectomized-sham hysterectomized (OSH) hamsters were tested for lordosis behavior following treatments including either 1, 5, or 10 micrograms estradiol benzoate (EB) in combination with 0.1, 0.25, and 0.5 mg progesterone. Few animals responded at the 1 microgram dose of EB and there were no differences in latency to the first display of lordosis or in the total lordosis duration among responding animals in the 5 and 10 micrograms EB groups. However, there was significantly more positive tests in the OSH group injected with 5 micrograms EB than in the OH group and this difference approached statistical significance in the 10 micrograms EB groups. The results are compared to similar studies in rats and possible mechanisms for the effects of hysterectomy are discussed.     

Sexual behavior of male and female septal lesioned rats

Gonadectomized male and female rats were given septal lesions (SL) or sham surgery at approximately 60 days of age. After 3 weeks lordosis behavior tests were initiated. Females were tested after daily injections of 2 μg estradiol benzoate (EB) for 3 days, while males were tested after EB only (2 μg×3 days), and after EB plus progesterone (Prog). The mean lordosis quotients (LQ) of septal lesioned female rats were significantly higher than those of sham operated controls. No increase in lordosis responding was seen in male rats with either EB alone or EB+Prog. Following an additional 3 week interval without steroid treatment masculine behavior tests began. All animals received a pretest and were tested again on Day 4, 7, 11 and 15 daily tesosterone propionate (150 μg/day) treatment. No alterations in masculine sexual behavior (relative to that of controls) were found in either male or female septal lesioned rats. It is concluded that the increased hormone sensitivity is specific for lordosis behavior, at least when the SL are given in adulthood.     

Bulbectomy and sensitivity to estrogen: Anatomical and functional specificity

In order to clarify the influence of the olfactory system on female sexual behavior, ovariectomized rats were given sham operations (SHAM), total bilateral olfactory bulbectomy (TBULBX), partial bulbectomy (PBULBX), anterior olfactory nucleus lesions (AON) or accessory olfactory bulb lesions (AOB), and tested for lordosis behavior. Only TBULBX resulted in increased sensitivity to estradiol benzoate (EB) in that lordosis quotients (LQ) were increased and rejection behavior decreased following administration of 2, 4 or 8 μg EB/kg/day for 3 days. Only TBULBX group rats were anosmic on 2 postoperative tests. TBULBX group rats showed very mild hyperresponsiveness on an emotionality test. Effects of TBULBX on LQ are not due to general sensory hyperresponsiveness or EB-induced hyperresponsiveness since no differences in the quality of lordosis occurred, and no differences occurred in latency to paw-lift on hot plate tests with or without EB. Heightened EB sensitivity in the TBULBX group is not due to adrenal steroids since following adrenalectomy and 8 μg EB/kg treatment, TBULBX group LQ scores were still elevated relative to those of SHAM controls. The LQ scores of PBULBX group rats were intermediate to those of SHAM and TBULBX group rats. Bulbectomy-induced alterations in sensitivity to EB as measured by the LQ do not appear to be due to alterations in “arousal” mechanisms in general. While deficits in olfactory perception might exacerbate the effect, it is unlikely that anosmia per se is sufficient to induce major alterations in the degree of sexual receptivity following EB. The magnitude of behavioral effects of bulbectomy on EB sensitivity may be related, to some extent, to the amount of bulb tissue removed. It is possible that bulbectomy may enhance behavioral sensitivity to EB by disrupting biochemical responses to EB in limbic system structures which normally exert an inhibitory influence over sexual receptivity.     

Deprivation of REM sleep in the rat and the opioid peptides beta-endorphin and dynorphin

Effects of 'rapid eye movement' sleep deprivation (REMd) on two opioid peptides, beta-endorphin and dynorphin, were studied in rats. Both peptides were measured by radioimmunoassay techniques. The level of beta-endorphin was estimated in the hypothalamus, in the anterior lobe of the pituitary and in the blood. The amount of dynorphin was estimated in the hypothalamus. REMd was induced for 72 h and achieved by two different methods, the platform technique and the pendulum technique. Three control groups were additionally run. As a consequence of REMd, an increase in beta-endorphin level was discovered in the blood plasma, while a small decrease was found in the hypothalamus. No changes could be detected for beta-endorphin levels in the pituitary or for hypothalamic dynorphin concentration. The deprivation effects are interpreted as belonging to a group of changes, all of which point to a small increase in tonic arousal as a result of REMd.     

Inhibitory and facilitatory neural mechanisms involved in the regulation of lordosis behavior in female rats: Effects of dual cuts in the preoptic area and hypothalamus

Two types of cuts were performed at a 4–5 week interval in the same ovariectomized rats; horizontal half-circle cut located just above the anterior commissure (ARD) and half-dome cut located anterior to the ventromedial nucleus (AD). Behavioral tests were carried out following the pretreatment with estradiol benzoate for 3 days and progesterone on the fourth day. When females received AD first (Experiment 1) the mean LQ was significantly lower than that of controls without brain surgery. Then, the AD rats were subjected to ARD or ARD sham. At the second test, the mean LQ of AD-ARD rats increased to the control level, but the LQ of AD-ARD sham rats was still low. In the experiment 2, the order of the brain surgery was just reversed. In the first test, all ARD females showed high levels of lordosis and the mean LQ was higher than that of control. Then, these ARD females receiving AD or AD sham were subjected to the second test. The mean LQ of ARD-AD rats decreased to the level of the control, but the LQ of ARD-AD sham rats was still high. Thus, dorsal neural inputs to or through the preoptic area and hypothalamus may exert inhibitory influences on a lordosis mediating system and anterolateral outputs of the medial basal hypothalamus appear to be concerned with a lordosis facilitating mechanism. These two systems seem to have a mutual correlation in regulating lordosis response. However, ARD or AD could not completely reverse the suppressive effect of AD or the facilitatory effect of ARD in the animals with dual cuts. It is suggested that the dorsal extrahypothalamic inhibitory influence and the hypothalamic facilitatory influence can regulate the display of lordosis independently in female rats.     

Synergistic action of estradiol, progesterone and testosterone on rat proceptive behavior.

The role of estradiol (E), progesterone (P) and testosterone (T) in the control of rat feminine sexual behavior (receptivity, proceptivity and sexual orientation) was analyzed. The action of estradiol benzoate (EB, 1.25 micrograms/rat x 3 days) and P (0.5 mg/rat) was compared in ovariectomized (OVX) and ovariectomized-adrenalectomized (OVX + ADX) subjects. Administration of EB alone was followed by maximum levels of lordosis behavior and a male-directed orientation in both OVX and OVX + ADX females. A reduction in the level of proceptivity was observed in EB-treated OVX + ADX animals as compared with EB-treated OVX rats. The administration of P to OVX + ADX females resulted in an increase in proceptive behavior similar to that observed in OVX EB-treated animals. A further study analyzed the effect of combined administration of EB, P and various doses of T (30, 90 and 270 micrograms/rat) in OVX + ADX rats. A synergistic action of all three hormones on proceptivity was observed. Neither a further increase in lordosis nor in male-directed orientation was observed in EB-treated females after additional treatment with P or T independently or together. Finally, we studied the effect of adrenalectomy on the spontaneous onset of estrous behavior. Adrenalectomy did not modify any aspect of normal feminine sexual behavior, suggesting that the adrenals, in the presence of the ovaries, are of no critical importance for this behavior. The possible contribution of adrenal steroids to the expression of proceptivity is discussed.     

Prolonged hormone deprivation and pretest cage adaptation as factors affecting the display of lordosis by female rats

Spayed females given no exogenous ovarian hormone for 60 days display relatively low lordosis quotients due to deprivation desensitiaztion, but a second injection 7 days later produces LQ scores within the normal range. Leaving females in the observation cage for 2 hr before introducing the stimulus male, and requiring 50 mounts by the male produces higher LQ scores than those obtained without cage adaptation. Cage adaptation tends to counteract the effects of deprivation desensitization.     

Sleep deprivation suppresses the increase of rapid eye movement density across sleep cycles

We investigated the association between rapid eye movement (REM) density (REMd) and electroencephalogram (EEG) activity during non‐rapid eye movement (NREM) and REM sleep, within the re‐assessment, in a large sample of normal subjects, of the reduction of oculomotor activity in REM sleep after total sleep deprivation (SD). Coherently with the hypothesis of a role of homeostatic sleep pressure in influencing REMd, a negative correlation between changes in REMd and slow‐wave activity (SWA) was expected. A further aim of the study was to evaluate if the decreased REMd after SD affects ultradian changes across sleep periods. Fifty normal subjects (29 male and 21 female; mean age = 24.3 ± 2.2 years) were studied for four consecutive days and nights. Sleep recordings were scheduled in the first (adaptation), second (baseline) and fourth night (recovery). After awakening from baseline sleep, a protocol of 40 h SD started at 10:00 hours. Polysomnographic measures, REMd and quantitative EEG activity during NREM and REM sleep of baseline and recovery nights were compared. We found a clear reduction of REMd in the recovery after SD, due to the lack of REMd changes across cycles. Oculomotor changes positively correlated with a decreased power in a specific range of fast sigma activity (14.75–15.25 Hz) in NREM, but not with SWA. REMd changes were also related to EEG power in the 12.75–13.00 Hz range in REM sleep. The present results confirm the oculomotor depression after SD, clarifying that it is explained by the lack of changes in REMd across sleep cycles. The depression of REMd can not simply be related to homeostatic mechanisms, as REMd changes were associated with EEG power changes in a specific range of spindle frequency activity, but not with SWA.