Diestrous Phase Research Articles

Inappropriate ovarian feedback in basal gonadotropin secretion in 4-day cyclic rat treated with mifepristone: Role of endogenous estradiol

Administration of the antiprogesterone RU486 to 4-day cyclic rats from metestrus onwards resulted in a dissociation of basal LH and FSH secretion and ovariectomy abolished this effect of RU486. Since RU486 also induces abnormally high concentrations of testosterone without affecting estradiol concentrations during the diestrous phase, we have studied the involvement of androgen or estrogen in RU486-dissociated gonadotropin secretions. Ovariectomized- (OVX) or sham-OVX rats at 08:00 h in metestrus were injected with RU486 (2 mg) or vehicle (0.2 ml) at 08:00 and 17:00 h in metestrus (day 1) and diestrus (day 2). Also, OVX-and sham-OVX rats injected with RU486 or oil were, in addition, treated with the antiandrogen flutamide and/or the antiestrogen tamoxifen (1 mg/0.2 ml) at 08:00 and 17:00 on days 1 and 2. The serum concentrations of LH and FSH were determined at 08:00 and 17:00 h on days 1 and 2 and at 08:00 h on day 3. OVX completely reversed the effects of RU486 on basal gonadotropin secretions while flutamide treatment affected neither LH nor FSH in any of the groups studied. On the contrary, tamoxifen treatment in RU486-injected rats reduced the LH concentrations to the levels found in OVX-rats and increased FSH concentrations to the levels in sham-OVX rats. Since the doses of flutamide and tamoxifen used block the action of androgens and estrogens, respectively, the results of this study evidence that endogenous estradiol in the absence of the effects of progesterone at both hypothalamus-pituitary and ovary levels stimulates LH and inhibits FSH secretion during the low secretion rate of gonadotropins in the rat.

Significance of high glucose-6-phosphatase activity in rat oviduct epithelium.

To study the origin of glucose in the oviduct fluid, we cytochemically examined glucose-6-phosphatase (G6Pase) activity in rat oviduct. The activity in the whole oviduct was also assayed biochemically. During proestrous, estrous, and metestrous phases, staining reaction for the activity was moderate in the epithelium of the caudal isthmus (CaI) and uterotubal junction (UJ), whereas it was weak in that of the ampulla (A) and cephalic isthmus (CeI). In the diestrous phase, staining reaction in the epithelium of CaI and UJ became strong although it remained weak in that of A and CeI. Reaction product for the activity was localized in the endoplasmic reticulum and nuclear envelope of all cell types in the epithelium. The amount of reaction product in secretory cells was small to moderate in CaI and UJ, and small in A and CeI during proestrus, estrus, and metestrus. In diestrous the amount became abundant in CaI and UJ and moderate in A and CeI. However, the amount in ciliated cells remained small in the four segments during the four phases. The biochemical activity in diestrous was greater than that in proestrus, estrus, or metestrus. This shows that the activity is high in secretory cells in the epithelium of CaI and UJ in the diestrous phase and suggests that the role of the high activity is to release glucose into the oviduct fluid for use by the embryo passing down the CaI and UJ to the uterus.

Modulation of hypothalamic galanin gene expression by estrogen in peripubertal rats

Hypothalamic galanin gene expression was investigated during reproductive maturation in peripubertal rats. Rat galanin-like immunoreactivity (rGAL-LI) increased in the median eminence and anterior pituitary during the extended first estrous and diestrous phases relative to anestrous phase female or male rats. In the neurointermediate lobe, rGAL-LI was elevated in first diestrous phase compared to anestrous phase females or males. In a second study, hypothalamic tissue was divided into quadrants for analysis of rat galanin (rGAL) mRNA by Northern blot hybridization. Two days after the injection of pregnant mare's serum gonadotropin (PMSG), rGAL mRNA increased approximately twofold in the paraventricular area and preoptic area quadrants. No effects of PMSG on galanin gene expression were found in medial basal or supraoptic hypothalamic quadrants. Because PMSG acts through the stimulation of ovarian estrogen secretion, these studies conclude that galanin gene expression in dorsal hypothalamic nuclei is under the stimulatory influence of estrogen and suggest that galanin may be a mediator of central ovarian steroid feedback.

The staggerer gene curtails the reproductive life span of females.

Three studies were undertaken to investigate some features of the reproductive activity of female staggerer mice of the C57BL/6 strain. It was found that in the staggerer female, (1) vaginal opening and onset of vaginal estrous cycling were delayed; (2) the vaginal estrous cycle was irregular and characterized by abnormally prolonged diestrous and estrous phases, and (3) the reproductive life span of the mutant female was confined to a 3-month period after puberty. The abnormalities observed in sexual functions suggest a specific influence of the staggerer gene on reproductive activity.

Studies on Regulatory Mechanisms for Gonadotropins Secretion in Lactating Rats

The present study was designed to clarify mechanisms responsible for regulation of FSH and LH secretion and ovarian follicular maturation during lactation in rats. Throughout lactation in rats, plasma levels of follicle-stimulating hormone (FSH) remain within the range normally found during the diestrous phase of the estrous cycle, regardless of litter size, although levels of luteinizing hormone (LH) in plasma are consistently lower in dams nursing 8 pups than in dams nursing 2 pups. All antral follicles larger than 401μm in diameter degenerate during the first half of lactation and do not reappear until the second half of lactation in rats nursing 8 pups. Healthy follicles of this size, however, are always present in mothers nursing 2 pups. These changes in follicular degeneration corresponded with a decrease in concentrations of plasma LH in the first half of lactation, and follicular development was noted with an increase in basal levels of plasma LH in the second half of lactation. Corpora lutea formed after postpartum ovulation secrete a large amount of progesterone under the influence of prolactin released as a result of suckling. Despite continued suckling, plasma concentrations of prolactin and progesterone decline gradually and a slight increase in plasma concentrations of estradiol-17β occurs during the second half of lactation. Concentrations of bioactive and immunoreactive inhibin in plasma vary with the number of healthy antral follicles and no positive correlation has been observed with luteal function throughout lactation in the rat.On the basis of the present results it is indicated that 1) tonic secretion of LH is an important factor in normal follicular maturation and maintenance in lactating rats, 2) the suckling stimulus, rather than ovarian factors, is mainly responsible for the suppression of FSH as well as LH secretion during the first half of lactation in rats nursing 8 pups. On the other hand, during the second half of lactation in rats nursing 8 pups, ovarian inhibin plays a primary role in the suppression of FSH secretion, whereas ovarian steroids act to suppress LH secretion. The present findings also indicate that 3) the suckling stimulus alone suppressed the secretion of both LH and FSH and this effect may be mediated by the inhibition of LH releasing hormone (LH-RH) secretion from the hypothalamus, 4) the suckling-induced inhibition of LH-RH may be primarily mediated by endogenous corticotropin-releasing hormone and opioid peptides and 5) the pituitary-adrenal system is capable of influencing the maintenance of a normal secretion of gonadotropins and prolactin as well as the maintenance of ovarian function during the lactation in the rat.

Variations in the hypothalamic-pituitary-adrenal response to stress during the estrous cycle in the rat.

To investigate the role of gonadal steroids in the hypothalamic-pituitary-adrenal (HPA) response to stress, we studied adrenocorticotrophin (ACTH) and corticosterone (B) responses to 20-min restraint stress in cycling female rats, and in ovariectomized (OVX) rats replaced with physiological levels of estradiol (E2) and progesterone (P). In cycling rats, we found significantly higher peak ACTH (P less than 0.01) and B (P less than 0.05) responses to stress during proestrus compared to the estrous and diestrous phases. No differences were found in either basal ACTH and B levels across the cycle phases. In a separate study, OVX rats were maintained on low, physiological levels of E2 and P with silastic implants for 3 days, and injected either with oil (O'), 10 micrograms of E2 (E') 24 h before stress testing, or with E2 and 500 micrograms P 24 and 4 h, respectively, prior to stress (EP'). These treatments mimicked endogenous profiles of E2 and P occurring during diestrous, proestrous, and late proestrous-early estrous phases, respectively. In response to stress, ACTH levels were higher (P less than 0.01) in the E' group compared to the EP' and O' groups. Although the peak B response was similar in all groups, the E' and EP' groups secreted more B after the termination of stress than did the O' group. Within the 20 min stress period, ACTH levels in the E' group were significantly (P less than 0.05) higher at 5, 10, and 15 min after the onset of stress, compared to the EP' and O' groups. Plasma B levels were significantly higher in the E' group at 5 and 10 min (P less than 0.05 and P less than 0.01, respectively) compared to the EP' and O' group. beta-endorphin-like immunoreactive responses to restraint stress were also significantly higher in the E' group compared to the EP' (P less than 0.05) and O' (P less than 0.01) groups. In contrast to the effect seen at 24 h, ACTH responses to stress 48 h after E2 injection in the E' group were comparable to O' animals. There was no effect of E2 on ACTH clearance, whereas B clearance was enhanced in E' treated animals vs. O'-treated animals. These results indicate that the HPA axis in the female rat is most sensitive to stress during proestrous. Such enhanced HPA responses to stress are limited to the early portion of proestrous, as progesterone appears to inhibit the facilitatory effects of estrogen on ACTH release during stress. Taken together, these results suggest an ovarian influence on both activational and inhibitory components of HPA activity.

Development of uterine adenomyosis after treatment with dopamine antagonists in mice

Development of uterine adenomyosis was studied in SHN mice treated with psychotherapeutic drugs, sulpiride and perphenazine, and gastroenteric drug, metoclopramide, which act as dopamine antagonists to increase prolactin release from the pituitary gland. Administration of these drugs twice daily for 40–70 or 40–90 days of age induced an elevation in serum level of prolactin. Furthermore, the treated mice showed a prolongation of metestrous plus diestrous phase and a high incidence of uterine adenomyosis compared with vehicle-treated control mice. These results indicate that hyperprolactinemia produced by continuous treatment with psychotherapeutic and gastroenteric drugs is responsible for the occurrence of irregular estrous cycles and the genesis of uterine adenomyosis in mice.

Exercise-Induced Ovarian Dysfunction in the Rat

The effect of treadmill running on estrous cycles was studied in the rat. Additional effects of cortisol acetate treatment and adrenalectomy were studied in both exercising and sedentary rats. Sedentary rats given the vehicle or cortisol acetate, or which had been adrenalectomized, all exhibited estrous cycles with diestrous phases that were uniformly less than 4 days. However exercising rats had extended estrous cycles; 50-62% of cycles were incomplete within 11 days and 78% of rats had cycles with diestrous phases that were more than 4 days long. There were no difference in duration of estrous cycles of running rats that received vehicle, received cortisol acetate, or had been adrenalectomized. We conclude that the running regimen resulted in a delay of the normal ovulatory period in rats, and that this effect of running was not affected by the presence or absence of glucocorticoids.

Estrous cycle irregularities in overfed rats

Hypothalamic and genetic obesities in rodents are usually associated with reproductive impairments, but the underlying etiology of the latter is not clear because of concomitant metabolic abnormalities in these animal models. In the present study metabolically intact rats were used and obesity was developed by offering the rats a cafeteria-type diet. Purina chow-fed animals were used as control. Cafeteria feeding was associated with hyperphagia and an increased brown adipose tissue (BAT) thermogenesis, in association with long estrous cycles ( p<0.01). The latter was accounted for by a long diestrous phase ( p<0.02). Replacement of the cafeteria diet with purina rat chow corrected the estrous cycle irregularities, as caloric consumption and body weight were reduced. We propose, as a working hypothesis, that reproductive functions are finely tuned with body temperature, and that an excess feeding-induced BAT thermogenesis may underlie the disruption in estrous cycle observed during overfeeding.

Preprogramming of luteal progestational function by preovulatory luteinizing hormone surge in cycling rats.

Effects of hCG and anti-ovine LH serum (aLH) administration at the time of the preovulatory LH surge on both luteal progesterone secretion and subsequent vaginal cyclicity were investigated. In control 4-day cycling rats, blood progesterone (P) increased from 0400 hr on estrus (E) to 2300 hr on metestrus (M), then declined to a low level by 1800 hr on diestrus (D). A single iv injection of hCG (1.25 or 5 IU) at 1900 hr on proestrus (PE) suppressed the metestrous rise in blood P levels and prolonged the diestrous phase, in a dose-dependent manner, without affecting the numbers of oocytes released at ovulation. Attenuation of the LH surge by a single iv injection of aLH (0.3ml) at 1900 hr on day PE also had a similar effect. Injections of 0.1 ml aLH (ip, every 11-12 hr) from 0800 hr, but not from 0000 hr, on day E in the rats pretreated with hCG on day PE elevated blood P levels, from days E through D, above the values measured in control animals. The lutein cells from rats treated with hCG on day PE were found, by electron microscopy, to be in the process of structural luteolysis at as early as 2300 hr on day M, whereas luteinization appeared still insufficient in the lutein cells from the LH surge-attenuated animals even at this stage. These results confirm a previous finding that tonic levels of LH secreted during the postovulatory period cause luteolysis of a new crop of corpora lutea, and suggest that the magnitude of the ovulatory LH surge preprogrammes luteal function not only by potentiating luteal ability to secrete P but also by determinig the timing of the expression of luteal sensitivity to the suppressing effect of LH. The prolonged diestrous phase accompanied by suppressed luteal function observed in the animals treated with hCG alone on day PE suggests that the magnitude of the LH surge is probably involved also in regulation of the subsequent follicular growth and estrogen secretion.

Roles of gender, gonadectomy and estrous phase in the analgesic effects of intracerebroventricular morphine in rats

Gender and gonadal function have previously been shown to influence the magnitude of analgesia following systemic morphine and opioid and nonopioid forms of swim analgesia with male rats displaying greater analgesia than female rats and gonadectomy reducing analgesic magnitude in both genders. These effects have been presumed to be centrally mediated. The present study evaluated the roles of gender, gonadectomy and estrous phase upon dose-response and time-response functions of analgesia following intracerebroventricular administration of morphine as measured by the tail-flick and jump tests. Sham-operated male rats displayed significantly greater magnitudes of peak and total analgesia following central morphine than sham-operated female rats on both nociceptive measures. This striking effect was reflected both in terms of magnitude and ED 50; while male rats displayed near-maximal analgesia at a 5 μg dose of morphine, female rats displayed moderate analgesia at doses as high as 40 μg of morphine. Castration produced small, but significant reductions in the magnitude of central morphine analgesia; the ED 50 of morphine analgesia, however, was not changed. Although female rats in either proestrous or estrous displayed significantly greater magnitudes of analgesia than ovariectomized rats or rats in a combined met-/di-estrous phase at some doses, the ED 50 of morphine analgesia was not significantly altered as functions of estrous phase or ovariectomy. The interaction of opiate receptors and gonadal steroid receptors is considered as one possible determinant of gender differences observed in the magnitude and potency of central morphine analgesia.

Corpus luteum progesterone secretion in rats undergoing pineal-mediated reproductive regression.

In nonseasonal breeders, such as the laboratory rat, the potentiation of the antigonadal action of light deprivation by olfactory bulbectomy is manifested, among other things, by a diminished secretion of testosterone in males and estradiol in females. Little is known about the actions of the pineal gland on progesterone secretion. Since secretion of the luteotrophic hormones (LH and PRL) decreases in blind-anosmic rats and because the rat corpus luteum exhibits different degrees of LH and/or PRL dependency, the purpose of these experiments was to study the corpus luteum progesterone secretion in both pseudopregnant and pregnant blinded-bulbectomized rats. Female rats blinded and bulbectomized at the age of 25 d showed at adulthood (75 d old) (1) estrous cycles longer than the regular 4-5 d in length exhibited by intact rats: 82.3 vs. 9.0% (P less than .01); (2) a decreased paired ovarian weight, 24.1 +/- 3.7 (nine) vs. 37.3 +/- 2.2 (ten) mg/100 gm BW (P less than .05), and lower plasma levels of LH on metestrus: 15.9 +/- 1.7 vs. 26.2 +/- 3.4 ng/ml (P less than .01). Pinealectomy, as previously reported, completely reversed the effects of dual sensory deprivation. In contrast to the clear antigonadal action of the pineal gland, which seems to affect the follicular component of the ovary through modifications in the rate of LH secretion, the production of progesterone by the corpus luteum remained almost unaffected. Although the duration of the diestrous phase in both pseudopregnancy and pregnancy was significantly longer in blind-anosmic rats than in intact ones (P less than .01), the serum levels of progesterone throughout both corpus luteum phases were identical.(ABSTRACT TRUNCATED AT 250 WORDS)

Sexual Behavior of Mares

Behavior during the estrous phase of the ovulatory cycle of the mare is analogous in most ways to that of estrous females of other species. Proceptive behaviors bring the mare into the proximity of the male and attract his attention. Positioning facilitates mounting, intromission, and ejaculation. Estrous signs appear to be more intense in the few days prior to ovulation than during the transition periods that separate the recurring estrous and diestrous phases. Sexual behavior is absent during diestrus. Detection of estrus in mares is problematic in that it requires the presence (or at least facsimile acoustic or tactile stimuli) or a stallion. Unexplained conditions such as silent or subestrus make reliable determinations even more difficult. The choice of methods for distinguishing estrous from nonestrous mares depends, among other factors, upon characteristics of individual mares, as well as the number of mares to be evaluated. Detection of true estrus--that is, sexual behavior that is associated with follicular growth and ovulation--is confounded by the occurrence of estrus-like behavior independent of gonadal stimulation. Seasonally anovulatory and ovariectomized mares may regularly solicit and accept copulation despite low or even no circulating levels of ovarian steroids. Instead, endocrine support of sexual behavior in these mares appears to be provided by adrenal cortical androgens and/or estrogens. A smaller percentage of pregnant mares may also show some signs of estrus but are not likely to be receptive to mating. The ability of the mare to dissociate sexual behavior from ovulation is unique among infraprimate species studied. The display of estrous behavior and willingness to copulate, even at times when conception is impossible, may have functional significance in promoting band cohesiveness in wild and feral populations. Even without copulation, continued motivation to remain in proximity to the band stallion may contribute to the stability of the social unit outside the ovulatory season.

Lactational performance, consummatory behavior, and suppression of estrous cyclicity in rats suckling underfed pups.

The role of pups' appetite in the regulation of maternal consummatory behavior (food intake of nursing mothers), lactational performance and postpartum diestrus was studied over a period of 45 days postpartum in rats chronically exposed to either underfed or normally fed pups. Experimental rats (n = 10) daily received 5 pups, 4-10-days-old, that had been deprived of food for the preceding 24 h while under the care of nonlactating foster mothers. Control rats (n = 10) received normally fed pups obtained daily from lactating foster mothers. Throughout the experimental period, the daily milk yield (estimated by litter weight gain), the intake of food and water by the mother, as well as the ratio of litter weight gain to mother's intake of food and water were all markedly higher in rats nursing underfed pups than in rats nursing normally fed pups. After a peak in lactation around Day 15 postpartum, experimental rats produced the same amount of milk during extended lactation as they did in the beginning of lactation, while control rats produced only half the amount of milk during extended lactation as they did in early lactation. Regardless of the nutritional state of the suckling pups, maternal body weight increased progressively over the first four weeks of lactation and remained unchanged during the time of extended lactation. The postpartum diestrus and the subsequent diestrous phase in the time of extended lactation were considerably longer in duration in rats that nursed underfed pups. On Day 45 of lactation, prolactin levels were higher and the adrenal glands were larger in experimental rats than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of nipple stimulation in the suppression of estrous cyclicity during extended lactation in the rat.

The role of nipple stimulation in the suppression of the estrous cycle during extended lactation was studied in rats subjected to either total, partial, or sham excision of the nipples. Each female cohabited with 4 pups, 4-14 days old, over a period of 70 days postpartum, during which vaginal smears were recorded daily. Initially, regardless of the presence of nipples, all rats exhibited a postpartum diestrus that lasted for 12-20 days. Intact females (bearing 6 pairs of nipples) continued to exhibit successive prolonged diestrous phases over 70 days of lactation. A comparable result was obtained with females bearing only the anterior pair of nipples, which, in a separate experiment, was found to be the most frequently suckled pair. However, females devoid of nipples resumed regular (4-day) estrous cycles between Days 12 and 27 postpartum, in spite of their continuous contact with pups. Thus, when lactation is prolonged beyond the normal time of weaning (Day 21 postpartum), stimulation of the nipples by sucking becomes indispensable for the continued arrest of the estrous cycle. The possible mechanisms underlying this phenomenon are discussed.

Daily administration of melatonin delays rat vaginal opening and disrupts the first estrous cycles: evidence that these effects are synchronized by the onset of light.

The effect of daily melatonin administration was investigated in the immature female rat. Starting on day 15 of age, 100 micrograms melatonin were injected sc at different times of the day in animals housed in 12 h of light, 12 h of darkness or 16 h of light, 8 h of darkness. Melatonin given 9-11 h after the onset of light in both lighting regimens resulted in a 10-day delay of vaginal opening, a dissociation of the relation between vaginal opening and first proestrus, and a disruption of the initial estrous cycles. The same dose of melatonin given at other times during the photoperiod had no effect on sexual maturation. GnRH secretion in melatonin-treated animals was decreased, as judged by 30% lower pituitary GnRH receptor number in animals killed after opening of the vagina. During the diestrous phases, plasma levels of LH, FSH, and 17 beta-estradiol were similar to those in control rats, but during proestrus, the surge of FSH was higher, and the peak of estradiol was higher and of a longer duration. This hormonal pattern suggests a build-up of hormones in secreting cells, which follows the lower incidence of proestrous phases in melatonin-treated rats. This build-up of FSH was indeed present, with higher concentrations in the pituitary during diestrus after melatonin treatment, while pituitaries removed during proestrus had lower contents of FSH. These results confirm that chronic melatonin administration delays sexual maturation of female rat, probably by retarding maturation of hypothalamic GnRH-producing cells. Thus, melatonin could modify basal GnRH secretion or pulsatile release. Pituitary and ovarian responsiveness do not seem to be affected, since proestrous surges of 17 beta-estradiol, LH, and FSH occur, albeit at a reduced frequency. The results also show that there is a window of maximum sensitivity to administration of melatonin 9-11 h after the onset of light, and that this window of sensitivity is synchronized by the onset of light. This raises the possibility that the abnormal presence of endogenous melatonin during this period of the day could induce abnormal sexual development.

Effect of vehicle on intrauterine absorption of gentamicin in cattle

An intrauterine (IU) infusion of 4 ml gentamicin solution (G) was administered in a water vehicle to 4 normal cycling and healthy cows and in a saline vehicle to 4 other cows during the diestrous phase (days 7–14) of the cycle. Infusion solution (IS) and blood samples were collected periodically postinfusion. G concentration was determined in plasma and IS by radioimmunoassay. Eighty-three and 18% of the infused G disappeared from the uterine lumen by 6 hours postinfusion on using water and saline vehicles, respectively. Total amounts of G reaching the blood stream were nearly the same during the 6 hours postinfusion period using water and saline vehicles. This suggested the possibility of retention of drug in uterine tissue using the distilled water vehicle.

Regulation of carcinogen metabolism in the rat ovary by the estrous cycle and gonadotropin.

The activity of 7,12-dimethylbenz[a]anthracene hydroxylase in the rat ovary is several times higher in the proestrous phase of the estrous cycle than in the estrous and metestrous plus diestrous phases. Administration of gonadotropin leads to a similar increase in the capacity of the ovary to metabolize xenobiotics. This variation in the activity of 7,12-dimethylbenz[a]anthracene hydroxylase during the estrous cycle may be related to the marked changes in the incidence of ovarian cancer during menopause and in women taking contraceptive pills.

Changes in pituitary LHRH incorporation during the rat estrous cycle, and in rats made anovulatory by various experimental procedures.

Variations in anterior pituitary incorporation of LHRH in various experimental conditions have been investigated by administering tritiated LHRH. The pretreatment of animals with unlabelled LHRH significantly decreased the isotope incorporation in the pituitary gland. On the other hand, the incorporating capacity of the glands appeared to significantly change in relation to the different phases of the estrous cycle, the higher grade of radioactivity being detectable during the diestrous and proestrous phases. However, the amount of 3H-LHRH incorporated in the pituitary gland of rats bearing different types of constant estrous-anovulatory syndrome did not present significant variations in relation to the procedures employed in sterilization. Only rats neonatally androgenized with 1250 micrograms testosterone propionate showed a marked decrease of the incorporating capacity of the pituitary. One can conclude that the variations in pituitary responsiveness previously demonstrated among rats with the same anovulatory states are independent of LHRH incorporating capacity of the pituitary.

Hypergravity induced prolonged diestrous in the rat can be prevented by bromergocryptine or by previous exposure to the same conditions — A “memory” effect

Female rats exposed to chronic moderate hypergravity (up to 2.3g) respond by a prolongation of their diestrous phase which resembles a pseudopregnancy. This reaction can be prevented by injection of bromergocrytine (E.C.) during the first few days of centrifugation, or by a previous 21 days of exposure of the rats to moderate hypergravity conditions followed by 36 days of exposure to 1.0g before re-exposure. A “memory” effect is suggested.