Responses of the hypothalamic-pituitary-adrenal axis to noradrenergic and hormonal stimulation in prenatally stressed rats

We studied the effects of maternal stress (the so-called prenatal stress, PS, provided by immobilization of pregnant female Wistar rats for 1 h daily during the 15–21st gestational days) on the corticosterone response in the blood plasma evoked by infusion of 10 μg noradrenaline bitartrate into the III cerebral ventricle or by injection of β-1-24-corticotropin in 3-month-old male and female offspring. The animals were bearing an intracerebroventricular stainless steel guide cannula implanted eight to nine days before the experiment, and a Silastic catheter inserted into the external jugular vein 24 h prior to the experiment. Blood samples were periodically taken from conscious unrestrained rats (before and then 30, 60 and 90 or 120 min after noradrenaline or corticotropin challenge). In the male offspring PS augmented and prolonged an increase in the plasma corticosterone level resulting from adrenergic stimulation of the hypothalamus, as compared with that in non-stressed animals. In prenatally stressed female offspring tested in diestrus, there was no response of the hypothalamic-pituitary-adrenal (HPA) axis to intracerebroventricular noradrenaline stimulation, in contrast to what was observed in the control. Prenatal stress did not modify the adrenal cortex responsiveness to corticotropin either in male or in female offspring. The results demonstrate differential effects of PS on the adrenergic activation of the HPA axis in males and females. A decrease in the acute HPA stress-responsiveness in prenatally stressed male rats, which was demonstrated in an earlier study, and the maintenance or even enhancement of this effect in prenatally stressed females are not likely to be connected with the state of hypothalamic adrenergic reactivity.     

Modifications of Reactions of the Hypothalamo-Hypophyseal-Adrenocortical System to Noradrenergic and Corticotropic Stimulations in Rats Subjected to Prenatal Hydrocortisone Treatment

We studied the reactions of the adrenal cortex to corticotropic and central noradrenergic stimulations in mature adult male and female rats which, in the final week of the prenatal period, developed under conditions of an artificial increase in the level of glucocorticoids in the maternal organism (everyday injections of 50 µg/kg of hydrocortisone acetate suspension to pregnant females). Experiments were carried out on unanesthetized offsprings of both sexes under conditions of free behavior; the level of corticosterone was repeatedly measured in the blood plasma with 30-min-long intervals within a 90 to 120 min period after injection of a stimulating agent. There was practically no adrenocortical reaction to infusion of adrenaline into the cerebral ventricle III in males whose mothers were injected with hydrocorticosterone acetate in the pregnancy period. At the same time, males born by intact mothers demonstrated a significant increase in the corticosterone level 30 min after the above-mentioned infusion. Noradrenergic stimulation increased the corticosterone concentration in the blood plasma in female offspring of both control and experimental groups, but the dynamics of reactions in females prenatally treated by hydrocortisone acetate demonstrated certain specificity (the reaction was longer, and the corticosterone level in the blood was higher even at the 90th min after noradrenaline infusion). At the same time, there were no changes in the sensitivity of the adrenal cortex to β-1-24-corticotropin either in males or in females of all observed groups. These results show that an artificial increase in the level of glucocorticoid hormones in the blood of a pregnant female and fetus modifies the noradrenergic reaction of the hypothalamo-hypophyseal-adrenocortical system, but the direction of the respective changes in offspring males and females is opposite to that observed in prenatally stressed animals.Neirofiziologiya/Neurophysiology, Vol. 37, No. 1, pp. 21–25, January–February, 2005.     

Chronic melatonin treatment and the hypothalamo-pituitary-adrenal axis in the rat: Attenuation of the secretory response to stress and effects on hypothalamic neuropeptide content and release

The pituitary-adrenal secretory response to acute and chronic stress, suppressibility of adrenocortical secretions by exogenous glucocorticoids, and hypothalamic content and in vitro release of the two major peptidergic activators of the hypothalamo-pituitary-adrenal (HPA) axis, corticotropinreleasing hormone (CRH) and arginine-vasopressin (AVP), were examined in rats receiving daily melatonin (MEL) injections coincident with the circadian increment of endogenous pineal and adrenocortical secretory activity. After 7 days of MEL administration, the rats displayed a significant attenuation of the adrenocortical secretory response to acute and chronic stress. Chronic MEL treatment also prevented the decline in adrenocorticotropic hormone (ACTH) release resulting from chronic stress exposure. Hypothalamic CRH content was significantly lower in rats receiving MEL treatment, while AVP remained largely unaltered; however, MEL administration counteracted the chronic stress-induced decrease in hypothalamic AVP content and in vitro release. When exposed to dexamethasone in vitro, hypothalamic explants from MEL-treated rats responded with a stronger suppression of CRH and AVP release than those originating from vehicle-injected animals. These observations indicate that MEL attenuates the adrenocortical response to stress and influences the biosynthesis, release and glucocorticoid responsiveness of hypothalamic ACTH secretagogues.     

The effect of "social stress" during rat pregnancy on the anxiety level of the progeny

Anxiety and locomotion were studied in offsprings of female rats subjected to everyday stress (one a day being displaced into another cage with pregnant rats) during the 3d stage of pregnancy. At the age of 1 month, the prenatally stressed rats had higher anxiety and lower locomotion in comparison with control animals. At the age of 3 month, the prenatally stressed females did not significantly differ from the control in the level of anxiety and locomotion, while the males demonstrated lower ambulation than the control animals.     

血管紧张素Ⅱ在紧张应激引起大鼠血压升高中的作用

实验在雄性Sprague Dawley大鼠上进行。实验动物被随机分为对照组、应激组和应激 腹腔注射卡托普利 (captopril)组。应激组大鼠每天给予电击足底结合噪声的应激刺激 ,每日 2次 ,每次 2h ,连续 15d ;应激 ipcaptopril组大鼠在给予应激刺激期间 ,经腹腔内注射captopril 5 0mg/kg d。实验结果观察到 ,15d后 ,三组大鼠平均尾动脉收缩压分别为 :对照组 16 32± 0 5 5kPa (n =7) ,应激组 19 75± 1 0kPa (n =8) ,应激 ipcaptopril组17 6 9± 1 0 7kPa (n =8)。应激 ipcaptopril组大鼠的尾动脉收缩压较对照组动物有显著升高 (P <0 0 5 ) ,但又显著低于应激组大鼠 (P <0 0 5 ) ;同时 ,三组大鼠下丘脑组织中AVP mRNA水平分别为 :对照组 7332 6 6± 5 2 2 6 5 (n =6 ) ;应激组 12 990 33± 15 33 5 8(n =6 ) ,应激 ipcaptopril组 10 6 15 5± 1410 49(n =6 )。应激 ipcaptopril组大鼠下丘脑组织中AVP mRNA水平较对照组有显著升高 (P <0 0 0 1) ,但又显著低于单纯应激组大鼠 (P <0 0 5 )。统计结果显示 :各组大鼠下丘脑组织中AVP mRNA水平与血压之间存在正相关关系 (P <0 0 0 1)。对照组大鼠在侧脑室注射 (icv)选择性血管升压素 (AVP)V1受体拮抗剂d(CH2 ) 5Tyr(Me)AVP 0 3μg后 ,其平均动脉压 (     

Differences in Behavioral Parameters of Long-Term Pain in Formalin Test at the Period of Sex Maturation in Prenatally Stressed Female and Male Rats

The effect of immobilization of pregnant rats was studied on parameters of the specific biphasic behavioral response (BBR) (patterns of flexion, shaking, licking, duration of the phases and of the interphase interval), of which the first phase characterizes the acute, while the second, he long-term pain in a nociceptive formalin test in the 40-day old female and male off-spring. The following was found: (1) an increase of intensity of patterns of flexion and shaking in the extremity injected with formalin at the second response phase and of the phase duration both in males and in females, (2) an increase of the licking pattern during the second phase and of the phase duration in males. Thus, the prenatal stress produced an increase of the pain sensitivity only at the long-term BBR phase; this increase was revealed in males from the patterns organized at the spinal and supraspinal levels, whereas in females, only at the spinal level. It was concluded that at the period of sex maturation, before the onset of sex maturity, the prenatally stressed males had more expressed damages in the behavioral parameters of the long-term pain in the formalin test, as compared with the prenatally stressed females. The comparative analysis of the response parameters allows suggesting the greater damage in males, then in females, of the inhibition process in the descending inhibitory system modulating nociceptive signals at the spinal cord level.     

Prenatal flutamide treatment eliminates the adult male rat's dependency upon vasopressin when forming social-olfactory memories.

The sexually dimorphic number of cells expressing arginine vasopressin (AVP) in the bed nucleus of the stria terminalis and the density of AVP fibers within the lateral septum appear to be organized by pre- and postnatal androgens. Social recognition behaviors are also sexually dimorphic and AVP-dependent. Whereas AVP antagonists prevent males from recognizing familiar intruders by olfactory investigation of the anal-genital area, they have no effect in females. To test the hypothesis that the male's dependency upon AVP to form social recognition memories begins prior to birth, we compared the effectiveness of an AVP antagonist to block social recognition in control males and females with that seen in male offspring whose mothers were treated prenatally with an androgen antagonist (flutamide). In an initial study we showed that while sexual experience may enhance social recognition in males, virgin males exhibit the ability to recognize conspecifics and are sensitive to the memory blocking actions of AVP antagonists. In a second experiment, pregnant rats were treated daily for the last 10 days of gestation with either flutamide (10 mg) or control vehicle. Within 12 h of birth, male offspring from flutamide litters were injected with either testosterone proprionate (50 microg TP) or vehicle control. AVP-antagonist treatment in adults eliminated the ability of control males to recognize familiar juvenile intruders, but had no effect on males exposed prenatally to flutamide, regardless of whether these males were treated with TP or vehicle on day 1 of life. These data support the hypothesis that the development of the male's dependency upon AVP to express social recognition memories begins with the organizational actions of prenatal androgens.     

Modification of expression of neurohormones in hypothalamus of prenatally stressed male rats in model of posttraumatic stress disorder

By the method of quantitative immunohistochemistry there has been studied expression of corticotrophin-releasing hormone (CRH) and vasopressin in hypothalamic paraventricular nucleus (PVN) of prenatally stressed rats in the experimental model of the posttraumatic stress disorder-the paradigm “stress-restress”. The prenatal stress was modeled by immobilization of pregnant female rats for 1 h from the 15th to the 19th day of pregnancy. It has been shown that in sexually mature males-descendants of stressed mothers-a decrease in immunoreactivity to CRH and vasopressin is observed in the parvocellular and magnocellular PVN areas 10 days after the restress. In the control group males born by intact mothers the level of immunoreactivity to CRH was increased in both PVN areas, whereas with respect to vasopressin-in the magnocellular area. Only in the prenatally stressed males there is detected a decrease in the corticosterone level in the blood plasma 10 days after the restress. It is concluded that in the control group males the manifestation of the pathological state in the paradigm “stress-restress” consists in hyperactivation of the hypothalamic chain of regulation of the hypothalamus-pituitary-adrenocortical system, whereas in the prenatally stressed animals, on the contrary, there is observed a decrease in activity both of the central (PVN) and of the peripheral (adrenal cortex) chain of this hormonal axis.     

Sex-dependent differences in parameters of long-term pain caused by inflammatory focus in prenatally stressed newborn rats

In experiments on the 7-day old female and male Long-Evans rat pups, for the first time, there was studied effect of prenatal (immobilization) stress on dynamics of nociceptive behavioral response caused by an inflammatory focus. The nociceptive sensitivity was evaluated for 1 h by the number of the flexion-shaking patterns organized at the spinal level in response to injection of formalin (10%, 10 μl) to the posterior leg sole. Control rat pups were not submitted to any prenatal stress; in these animals the response in the formalin test was found to be represented by one phase. It the prenatally stressed rat pups the studied patterns were organized into two phases characteristic of the definitive type of response. At the period between them (during interphase), the nociceptive behavior was absent. At the second, tonic phase the number of flexion-shakings in the prenatally stressed males was statistically significantly higher than in the prenatally stressed females, which indicates a sensitization of the neurons involved in the tonic pain chains in male individuals. Thus, the data obtained on prenatally stressed animals confirm the previous data about immaturity of the mechanisms mediating the second phase of response in the formalin test in the 7-day old rat pups. An important fact is revealed which indicates that in the prenatally stressed rat pups of the same age the second phase of response is already obvious. Mechanisms underlying the behavioral response caused by the inflammatory focus in the formalin test in the one-week old stressed rat pups are characterized by sexual dimorphism: the pain sensitivity in males at the second phase of response is statistically significantly higher than in females.     

Sex-dependent differences in parameters of a long-term pain caused by inflammatory focus in prenatally stressed newborn rats

In experiments on the 7-day-old female and male Long-Evans rat pups, for the first time, there was studied effect of prenatal (immobilization) stress on dynamics of nociceptive behavioral response caused by an inflammatory focus. The nociceptive sensitivity was evaluated for 1 h by the number of 7-day-old organized at the spinal level in response to injection of formalin (10%, 10 microl) to the posterior leg sole. Control rat pups were not submitted to any prenatal stress; in these animals the response in the formalin test was found to be represented by one phase. It the prenatally stressed rat pups the studied patterns were organized into two phases characteristic of the definitive type of response. At the period between them (during interphase), the nociceptive behavior was absent. At the second, tonic phase the number of flexes+shakes in the prenatally stressed males was statistically significantly higher than in the prenatally stressed females, which indicates a sensitization of the neurons involved in the tonic pain chains in male individuals. Thus, the data obtained on prenatally stressed animals confirm the previous data about immaturity of the mechanisms mediating the second phase of response in the formalin test in the 7-day-old rat pups. An important fact is revealed which indicates that in the prenatally stressed rat pups of the same age the second phase of response is already obvious. Mechanisms underlying the behavioral response caused by the inflammatory focus in the formalin test in the number flexes + shakes old stressed rat pups are characterized by sexual dimorphism: the pain sensitivity in males at the second phase of response is statistically significantly higher than in females.     

Prenatal stress alters circadian activity of hypothalamo-pituitary-adrenal axis and hippocampal corticosteroid receptors in adult rats of both gender.

Prenatal stress impairs activity of the hypothalamo-pituitary-adrenal (HPA) axis in response to stress in adult offspring. So far, very few data are available on the effects of prenatal stress on circadian functioning of the HPA axis. Here, we studied the effects of prenatal stress on the circadian rhythm of corticosterone secretion in male and female adult rats. To evaluate the effects of prenatal stress on various regulatory components of corticosterone secretion, we also assessed the diurnal fluctuation of adrenocorticotropin, total and free corticosterone levels, and hippocampal corticosteroid receptors. Finally, in the search of possible maternal factors, we studied the effects of repeated restraint stress on the pattern of corticosterone secretion in pregnant female rats. Results demonstrate that prenatal stress induced higher levels of total and free corticosterone secretion at the end of the light period in both males and females, and hypercorticism over the entire diurnal cycle in females. No diurnal fluctuation of adrenocorticotropin was observed in any group studied. The effects of prenatal stress on corticosterone secretion could be mediated, at least in part, by a reduction in corticosteroid receptors at specific times of day. Results also show that prepartal stress alters the pattern of corticosterone secretion in pregnant females. Those data indicate that prenatally stressed rats exhibit an altered temporal functioning of the HPA axis, which, taken together with their abnormal response to stress, reinforces the idea of a general homeostatic dysfunction in those animals.     

Characterization of depression-like behavior in prenatally stressed female rats during ovary cycle

The aim of the present work was a comparative analysis of dynamics of depression-like behavior in prenatally stressed and non-prenatally stressed female rats in the key phases of the ovary cycle. It was found that non-stressed female rats demonstrated high level of depression-like behavior in proestrous phase as compared to the diestrous phase, whereas these rats showed low level of depression-like behavior in estrous phase in Porsolt's test. On the contrary, there were no significant differences in extent of depression-like behavior between prenatally stressed rats in the diestrous and proestrous, although in the phase of estrous in these animals an increase in level of depression-like behavior was noted. Thus, the results of this study indicated pronounced effects of prenatal stress on the character of depression-like behavior of females in different phases of ovary cycle. This study revealed leveling and reversed action of prenatal stress on depression-like behavior in key phases of sexual cycle in female rats.     

Factors modifying the effect of diazepam on plasma corticosterone levels in rats

We have examined factors that alter the effect of diazepam (DZ) on plasma corticosterone (CS) in rats. DZ had a biphasic effect on plasma CS levels: CS decreased with doses below 5 mg/kg and increased with higher doses. Peak response occurred 90 minutes post injection in both sexes. Plasma DZ levels were significantly higher in females than in males and peak at 10 and 30 minutes post injection in males and females, respectively. There was also a sex difference in the pattern of DZ metabolites. An acute stressor (30 minutes of immobilization) did not affect plasma CS levels in rats injected with a 5 mg/kg dose of DZ. Prenatally stressed animals did not differ in basal CS levels or in their response to 5 mg/kg of DZ compared to prenatally non-stressed animals. These two groups of animals also did not differ in plasma levels of DZ or of its metabolites. By contrast, the 5 mg/kg dose of DZ had no effect on plasma testosterone levels in control animals, but increased it in prenatally stressed animals. Furthermore, compared to non-stressed controls, prenatally stressed animals had lower baseline plasma testosterone levels. These results indicate that the effect of DZ on plasma CS is influenced by endogenous as well as exogenous factors and that these effects vary with the particular biochemical parameter under examination.     

Prenatal stress impairs maternal behavior in a conflict situation and reduces hippocampal benzodiazepine receptors

Maternal behavior (pup retrieval) was assessed in prenatally stressed rats during control and conflict situations (having to pass through an airstream) when their pups were 4-5 days old. There was no difference in pup retrieval between experimental and control rats under normal conditions but only 52% of the former retrieved their pups during the conflict situation, compared with 96% of the controls. Catecholamine (CA) levels in the arcuate nucleus (Arc.n.) and noradrenaline in the medial preoptic nucleus (POM) were not altered in prenatally stressed females, but their dopamine levels in the POM tended to be lower (p less than 0.1). The number of benzodiazepine (BZ) receptors in the hippocampi of prenatally stressed females was significantly lower than in controls. We conclude from these results that random prenatal noise and light stress increases the vulnerability to stressful situations in the female offspring during adulthood, which may be accompanied by altered CA function in the hypothalamus and BZ binding in the hippocampus.     

Vasopressin and A1 noradrenaline turnover during food or water deprivation in the rat

In the present study, we have examined in Wistar rats the effects of food or water deprivation of 3 days on the hypophyso-adrenal axis, vasopressinergic system and activity of A1 noradrenergic brain stem cell group, which is involved in the control of the hypothalamic neuro-endocrine activity. Levels of adrenocorticotropic hormone (ACTH) and vasopressin (AVP) were determined by radio-immunoassay, and corticosterone level was determined by fluorimetric method. Plasma levels of ACTH and corticosterone were greatly increased in both groups of rats. In water-deprived rats, plasma AVP (13.83 +/- 1.63 vs. 3.03 +/- 0.23 pg/ml) and osmolality levels were significantly elevated with a marked decrease of AVP hypophysis content (272 +/- 65 vs. 1098 +/- 75 ng/mg protein), but not in food-deprived rats in which osmolality did not change and AVP remained stocked (2082 +/- 216 ng/mg protein) in the hypophysis without release in the plasma (1.11 +/- 0.23 pg/ml). These observations indicated that both food-deprivation and water-deprivation stimulated the pituitary adrenal axis thereby suggesting a stress state. AVP production is stimulated both by fluid and food restriction but is secreted with differential effects: during food restriction AVP secretion is limited to supporting the hypothalamic pituitary-adrenal system.     

Response of the hypothalamo-neurohypophyseal axis (AVP system) and the kidney to salt load in young propylthiouracil-treated rats

The development of the ability of the kidney to concentrate urine was studied in normal and propylthiouracil-treated rats by measuring urinary sodium concentration and osmolarity at different ages. It was shown that the normal animals, but not the PTU-treated ones were able to concentrate urine at 35 days of age. The response of the hypothalamo-neurohypophyseal axis (AVP system) and that of the kidney were investigated in the two categories of animals at 35 days of age by measuring concomitantly the AVP content of the hypothalamus and neurohypophysis, the AVP plasma concentration and the natremia and plasma osmolarity at various intervals after intraperitoneal injection of a 5% NaCl solution. In normal, as well as in PTU-treated rats, salt load did not lead to significant modifications of the hypothalamic AVP content. In comparison with normal rats, the neurohypophysis of the PTU-treated ones released AVP more slowly, but with a similar amplitude. In normal rats, the plasma AVP concentration was already maximal 30 min after salt load and then decreased and returned to the normal value at 2 hrs; at the same time, the natremia and plasma osmolarity also recovered their normal value. In contrast, the plasma AVP concentration as well as the natremia remained high 1 h 30 after salt load in PTU-treated rats. It is concluded that PTU-treated young rat is unable to compensate the salt load in normal delays. Beside the slowing in AVP release by neurohypophysis and decreased AVP plasma level, the responsiveness of the kidney seems to be altered.     

Effects of prenatal ethanol exposure and sex on the arginine vasopressin response to hemorrhage in the rat

AVP synthesis, storage, and osmotically stimulated release are reduced in young adult rats exposed prenatally to ethanol (PE). Whether the reduced release of AVP to the osmotic stimulus is due to impairment of the vasopressin system or specifically to an osmoreceptor-mediated release is not known. The present experiments were done, therefore, to determine whether a hemorrhage-induced AVP response would also be diminished in PE-exposed rats. Pregnant rats were fed either a control liquid diet [no prenatal ethanol (NPE)] or a liquid diet with 35% of the calories from ethanol from days 7-21 of pregnancy. Offspring were weaned at 3 wk of life. At 11 wk of age, femoral arterial catheters were surgically placed, and blood volumes were determined at 12 wk. Three days later, two hemorrhages of 10% of the blood volume were performed with samples taken before and 10 min after the hemorrhages. After a 20% blood loss, plasma AVP was 19% higher in NPE rats than in the PE rats despite no differences in mean arterial blood pressure (MABP). Also, hypothalamic AVP mRNA and pituitary AVP content were reduced in PE rats. Furthermore, confirming an earlier report of sex differences in AVP release, the hemorrhage-induced hormone response was twofold greater in female rats than male rats, regardless of previous ethanol exposure. These studies demonstrate that the AVP response to hemorrhage is reduced in PE rats independently of differences in MABP. The data are compatible with a theory of a reduced number of hemorrhage-responsive vasopressinergic neurons capable of stimulated AVP release in PE rats.     

Prenatal Amphetamine-Induced Dopaminergic Alteration in a Gender- and Estrogen-Dependent Manner

Prenatal exposure to amphetamine induces changes in dopamine receptors in mesolimbic areas and alters locomotor response to amphetamine during adulthood. Sex differences have been reported in amphetamine-induced brain activity and stress sensitivity. We evaluated the effects of prenatal amphetamine exposure on locomotor activity, dopamine receptors and tyrosine hydroxylase mRNA expression in nucleus accumbens and caudate-putamen in response to amphetamine challenge in adult female and male rats. The role of estrogen in the response to restraint stress was analyzed in ovariectomized, prenatally amphetamine-exposed rats. Pregnant rats were treated with d-amphetamine during days 15–21 of gestation. Nucleus accumbens and caudate-putamen were processed for mRNA determination by real-time PCR. In nucleus accumbens, higher mRNA dopamine (D3) receptor expression was found in basal and d-amphetamine-challenge conditions in female than male, and prenatal amphetamine increased the difference. No sex differences were observed in caudate-putamen. Basal saline-treated females showed higher locomotor activity than males. Amphetamine challenge in prenatally amphetamine-exposed rats increased locomotor activity in males and reduced it in females. In nucleus accumbens, estrogen diminished mRNA D1, D2 and D3 receptor expression in basal, and D1 and D3 in ovariectomized stressed rats. Estrogen prevented the increase in tyrosine hydroxylase expression induced by stress in ovariectomized prenatally exposed rats. In conclusion, estrogen modulates mRNA levels of D1, D2 and D3 receptors and tyrosine hydroxylase expression in nucleus accumbens; prenatal amphetamine-exposure effects on D3 receptors and behavioral responses were gender dependent.

     

Influence of age, sex and hypoxia on plasma dopamine-beta-hydroxylase activity in the rat

Using rats (Wistar strain) of our own breed, we studied dopamine-beta-hydroxylase (E.C. 1.14.17.1) (DBH) activity in the plasma of animals of different ages (in correlation to sex) under normal conditions and after exposure to altitude hypoxia (corresponding to 7000 or 9000 m and lasting 20 min). The enzyme was determined by the method of Kato et al. (1974). We found that the given plasma enzyme activity was significantly higher in females than in males, throughout the whole life-span. In addition, we found that minimum activity was reached on about the 14th and 21st day of postnatal life and again on the 40th day, while maximum activity was recorded at the ages of 5, 30 and 35 days and in adult rats. In adult animals (males and females), exposure to altitude hypoxia was followed by a statistically significant increase in plasma DBH activity, which was much more pronounced in females than in males. In males, 240 min after terminating hypoxia plasma DBH activity had returned to normal, but in females it was still significantly raised; after 48 h, plasma DBH activity in females was identical to the activity before exposure to hypoxia. In rats aged 5 and 35 days, hypoxia evoked a fluctuating response. A decrease in activity immediately after terminating hypoxia was followed at 60 min by a return to normal, but at 240 min there was again a significant decrease. In 21-day-old rats, hypoxia did not induce any significant change in plasma DBH activity (the initial activity level in this group was very low).     

Prenatal stress reduces fertility of male offspring in mice, without affecting their adult testosterone levels

The male offspring of mice stressed by crowding during the final third of pregnancy showed reductions in sexual behavior and fertility. When paired with receptive females, their latencies to mount and to achieve intromission and ejaculation were greater than controls, and 30% of them failed to ejaculate in the 100-min test. When housed continuously for 4 days with females, 31% of them failed to impregnate their partners, compared with 4% of controls. The sexual receptivity of the untreated females paired with prenatally stressed males was not affected. Resting testosterone levels of prenatally stressed males did not differ from those of controls, and the pattern of rise and fall of testosterone during a 60-min interaction with a female showed only minor differences. The results suggest a central, rather than peripheral, mediation of the behavioral effects of prenatal stress.