The effects of neonatal gonadectomy and prenatal stress on cortical thickness and asymmetry in rats

In Study I measures of cortical thickness were taken in 90-day-old male and female Sprague-Dawley, Wistar, and Long-Evans rats that were born to pregnant females shipped to the laboratory in late pregnancy and that were either gonadectomized at birth or left intact. No evidence for hemispheric differences in cortical thickness was found in any of the groups. Gonadectomy resulted in increased cortical thickness in male Sprague-Dawley and Wistar rats and in small increases in thickness of the left hemisphere in Long-Evans rats, especially males. No effects of gonadectomy were found in females of any strain. The lack of the expected right-over-left difference in cortical thickness in intact males may have been due to prenatal stress caused by housing, handling, and shipping. In Study 2 measures of cortical thickness were taken in 90-day-old male and female Sprague-Dawley rats that were bred in our laboratory, but otherwise similarly treated at birth. In this second study, the expected right-over-left hemispheric difference in cortical thickness was found in intact male rats; none was found in gonadectomized males or in either of the female groups. The lack of asymmetry in gonadectomized males appeared to be due to an increase in thickness in the left hemisphere. Taken together these studies provide support for the idea that hormones of testicular origin suppress cortical enlargement in the perinatal period, particularly in the left hemisphere.     

Brown adipose tissue redox status in response to dietary-induced obesity-associated oxidative stress in male and female rats

Obesity is linked to systemic oxidative stress and, although brown adipose tissue (BAT) plays a crucial role in energy balance, BAT redox status effects on obesity have not been studied previously. Female rats exhibit a greater BAT thermogenic capacity, attributed to enhanced mitochondrial differentiation, than males. The aim of this study was to investigate whether the mitochondrial sexual dimorphism is related to differences in BAT redox status and to assess its role in the regulation of body weight gain in response to chronic high fat diet (HFD) feeding. Ten-week-old Wistar rats of both genders were fed a pelleted control diet or HFD for 26 weeks. Although mitochondria of female rats produced higher levels of hydrogen peroxide than those of males, females exhibited lower oxidative damage, attributed to greater glutathione peroxidase activity and higher glutathione content. In response to HFD, body weight increased markedly in females, but oxidative capacity increased only in males, thus maintaining improved BAT redox status compared with females. In conclusion, the sexual dimorphism in BAT redox status found in control animals is attenuated by the HFD. The enhanced oxidative capacity of HFD males can be related to their greater resistance to body weight gain.     

Predictability of chronic intermittent stress: effects on sympathetic-adrenal medullary responses of laboratory rats

This experiment involved an examination of sympathetic-adrenal medullary responses of laboratory rats following exposure to chronic intermittent stress. Animals were assigned at random to one of three groups: (i) controls, handled briefly each day; (ii) restraint stress (RS), restrained for 30 min per day; or (iii) variable stress (VS), exposure to restraint, cold swim, or intermittent footshock during one of five time periods each day. On the 26th day, rats were prepared with chronic tail artery catheters for remote sampling of blood and direct measurement of mean arterial pressure and heart rate. On Day 28, rats of each group were exposed to 30 min of restraint stress and timed blood samples were collected and later analyzed for content of norepinephrine (NE) and epinephrine (EPI). VS rats gained significantly less body weight compared to control and RS rats. Basal measures of blood pressure and heart rate and of plasma NE and EPI were comparable for rats of the three groups. The plasma catecholamine responses to restraint stress on Day 28 were significantly reduced in RS and VS rats compared to first-time stressed controls. These findings suggest that predictability of the type of stressor and the time of its occurrence does not influence the pattern of diminished sympathetic-adrenal medullary responses of animals exposed to chronic intermittent stress.     

Alcohol-induced changes in mood and activation in males and females as related to catecholamine excretion and blood-alcohol level

Abstract.— Effects of a moderate dose of whisky (0.72 g ale/kg body weight) were studied in a male and a female group. Successive measurements of blood-alcohol concentration, catecholamine excretion, heart rate, and subjective reactions were made over a seven-hour period. Maximum blood-alcohol values as well as the disappearance rate of alcohol from the blood were significantly higher in the females than in the males. Adrenaline excretion was approximately the same in both groups during the control condition, but was significantly higher in the female group during the alcohol condition. Ratings of subjective reactions indicated that pleasant effects were more pronounced in the males, negative effects more marked in the females.     

Acute stress persistently enhances estrogen levels in the female rat

Here we tested whether exposure to either tailshock or swim stress alters ovarian hormone levels, estrogen and progesterone, in females and whether the effects are persistent. Adrenal hormone levels were also measured in males and females. Estradiol levels were elevated in unstressed females during proestrus relative to females in other stages of estrous, and exposure to the stressors enhanced estradiol beyond basal levels. For females stressed during diestrus 2, estradiol levels were elevated immediately after stressor cessation and up to 24 hrs. Exposure to tailshock, but not swim-stress, transiently enhanced progesterone in females stressed during the stage of proestrus and estrus. Glucocorticoid levels were elevated in response to both stressors and were supraelevated in females under both basal and stress conditions relative to males, particularly in blood from females exposed to acute swim stress. These results indicate that exposure to a relatively acute stressful event immediately and persistently enhances serum estradiol and are discussed in the context of reports that exposure to the same stressors immediately and persistently impairs associative learning in the female rat.     

Gender differences in acute and chronic stress in Wistar Kyoto (WKY) rats.

While females are considered more susceptible to depressive behavior, this assertion is not strongly supported by the experimental literature. Since stress contributes to depressive behavior, male and female Wistar Kyoto (WKY) rats were exposed to either one session (acute stress) or 5 sessions (chronic stress) of restraint plus cold in order to study depressive behavior in male and female rats. After their respective treatment exposure, rats were tested in the open field test (OFT) and for retention of a passive-avoidance (P-A) task. One stress session resulted in significant immobility in the OFT for males, whereas 5 sessions were required to produce similar immobility in female rats. Acute stress interfered with the retention of the P-A response for males, while both acute and chronic stress produced poor P-A responses in female rats. Food consumption decreased progressively, as a function of stress sessions, in female rats, whereas feeding in males returned to control levels after five stress days. Both acute and chronic stress exacerbated the stress ulcer response in male rats, but not in female rats. Chronic, but not acute, stress resulted in an increase in serotonin transporter mRNA levels in the dorsal raphe nucleus of both male and female rats. The general consensus from these data suggested that female rats were more vulnerable to chronic stress and consequently supported the notion that females may be more susceptible to stress-induced behavioral depression. Key Words: WKY rats, acute and chronic stress, gender, passive avoidance, open field behavior, stress-ulcer, adrenal weight, serotonin, dorsal raphe nucleus     

Altered grooming responses to stress in rats exposed prenatally to ethanol

The effects of prenatal alcohol exposure on grooming, locomotion, and rearing in response to stress were examined in adult rats whose mothers consumed a liquid diet containing 35% ethanol-derived calories (EDC). Offspring of both pair-fed 0% EDC mothers and ad libitum chow-fed mothers were included as controls. In Experiment 1, females groomed more than males following placement into a novel test chamber, but no differences due to prenatal treatment were observed. Ethanol-exposed animals groomed more than controls following the stress of a forced 1-min swim (Experiment 2), but when rats tested in Experiment 1 were observed again after forced swim stress (Experiment 3), no differences due to prenatal treatment or sex were observed. Experiment 4 examined the effects of pretreatment with 1 mg/kg naloxone on novelty-induced grooming and as in Experiment 1 prenatal treatment did not affect grooming responses. Females again groomed significantly more than males and naloxone reduced grooming equally for all groups. The results suggest that novelty-induced grooming is a sex-influenced behavior, with females grooming more than males, and that animals exposed prenatally to alcohol and tested as adults may have altered responses to certain stressors (i.e., forced swim) under specific conditions. The altered grooming response of alcohol-exposed rats to swim stress can be eliminated by preexposing them to novelty stress.     

Sex-dependent changes induced by prenatal stress in cortical and hippocampal morphology and behaviour in rats: an update

Recent prospective studies have shown that gestational stress in humans is more likely to cause cognitive and emotional problems in the offspring if it occurs during weeks 12-20 of pregnancy. There are also suggestions that such problems may be gender dependent. This review describes recent studies that found sex differences in the behaviour and brain morphology of rats stressed prenatally during the equivalent period of neuronal development in humans. Learning deficits are more prevalent in males and anxious behaviour in females but their appearance depends also on the timing and intensity of the stress and the age when the offspring were tested. Cognitive deficits and anxiety are linked to a sex-dependent reduction in neurogenesis and in measures of dendritic morphology in the prefrontal cortex and hippocampal formation. Maternal adrenalectomy prior to the stress prevents the anxiety in both sexes and learning deficits in males. Corticosterone administration to the dam to mimic levels induced by stress reinstates only the anxiety, indicating that it arises from foetal exposure to corticosterone from the maternal circulation. Learning deficits in males may result from a combination of a reduction in testosterone and in aromatase activity, together with the action of other adrenal hormones.     

Body dissatisfaction and body comparison with media images in males and females

This study examined the role of media body comparison as a mediator of the relationships between psychological factors and sociocultural pressures to be thin and body dissatisfaction in both females and males. Participants were 1,386 females (mean age = 19.37 years) and 1,130 males (mean age = 19.46) from diverse backgrounds who completed a self-report questionnaire. Path analysis was used to test a cross-sectional model in which media body comparison mediated the impact of self-esteem, depressive mood, parent dieting environment, friend dieting, TV exposure, magazine message exposure, weight teasing and body mass index (BMI) on body dissatisfaction. In females, media body comparison partially or fully mediated relationships between self-esteem, depressive mood, friend dieting, magazine message exposure and BMI, and body dissatisfaction. In males, media body comparison was not a significant predictor of body dissatisfaction. This research particularly highlights the need to further examine processes that are involved in the development of body dissatisfaction in males.     

A longitudinal investigation of the mediating role of self-esteem and body importance in the relationship between stress and body dissatisfaction in adolescent females and males

Body dissatisfaction is particularly prevalent during adolescence and has recently been linked to stress in females and males. However, prospective studies are needed to better understand the relationship between stress and body dissatisfaction. The present study investigates the direction of this association and the mediating role of self-esteem and body image importance. A sample of 298 adolescent females and males in Grades 7 to 10 (ages 12 to 17 years) were surveyed at two time points over a one-year period. Hierarchical regression analyses revealed that stress significantly predicted body dissatisfaction one year later. Furthermore, a multiple mediation analysis controlling for gender revealed a significant indirect effect in both cross-sectional and longitudinal models, indicating that stress predicts reductions in self-esteem and increases in body importance, which in turn predict body dissatisfaction. These findings suggest that stress, self-esteem, and body importance should be included in programmes aimed at improving body dissatisfaction.     

Gender differences in acute and chronic stress in Wistar Kyoto (WKY) rats

While females are considered more susceptible to depressive behavior, this assertion is not strongly supported by the experimental literature. Since stress contributes to depressive behavior, male and female Wistar Kyoto (WKY) rats were exposed to either one session (acute stress) or 5 sessions (chronic stress) of restraint plus cold in order to study depressive behavior in male and female rats. After their respective treatment exposure, rats were tested in the open field test (OFT) and for retention of a passive-avoidance (P-A) task. One stress session resulted in significant immobility in the OFT for males, whereas 5 sessions were required to produce similar immobility in female rats. Acute stress interfered with the retention of the P-A response for males, while both acute and chronic stress produced poor P-A responses in female rats. Food consumption decresed, progressively, as a function of stress sessions, in female rats, whereas feeding in males returned to control levels after five stress days. Both acute and chronic stress exacerbated the stress ulcer response in male rats, but not in female rats. Chronic, but not acute, stress resulted in an increase in serotonin transporter mRNA levels in the dorsal raphe nucleus of both male and, female rats. The general consensus from these data suggested that female rats were more vulnerable to chronic stress and consequently supported the notion that females may be more susceptible to stress induced behavioral depression.     

Effects of voluntary wheel running on heart rate, body temperature, and locomotor activity in response to acute and repeated stressor exposures in rats

Stress often negatively impacts physical and mental health but it has been suggested that voluntary physical activity may benefit health by reducing some of the effects of stress. The present experiments tested whether voluntary exercise can reduce heart rate, core body temperature and locomotor activity responses to acute (novelty or loud noise) or repeated stress (loud noise). After 6 weeks of running-wheel access, rats exposed to a novel environment had reduced heart rate, core body temperature, and locomotor activity responses compared to rats housed under sedentary conditions. In contrast, none of these measures were different between exercised and sedentary rats following acute 30-min noise exposures, at either 85 or 98 dB. Following 10 weeks of running-wheel access, both groups displayed significant habituation of all these responses to 10 consecutive daily 30-min presentations of 98 dB noise stress. However, the extent of habituation of all three responses was significantly enhanced in exercised compared to sedentary animals on the last exposure to noise. These results suggest that in physically active animals, under some conditions, acute responses to stress exposure may be reduced, and response habituation to repeated stress may be enhanced, which ultimately may reduce the negative and cumulative impact of stress.     

Effects of body mass and body image on exercise motives in adolescence

Objective. The objective was to examine age and gender differences in the effects of body mass and body image on exercise motives in adolescents. It was specifically predicted that weight management motive would be explained by body mass index in males, and by body size discrepancy in females, but this pattern would be less pronounced in younger than in older adolescents.Design. The design was a cross-sectional comparative study.Method. Participants comprised younger (11–13 years) and older (17–19 years) males and females (N=180). They completed measures of exercise participation, exercise motives, and perceived and ideal body size. Height and weight were also measured. Hierarchical regression analyses were conducted, separately for younger males, younger females, older males and older females. In each analysis, the dependent variable was an exercise motive, and the independent variables were, in order of entry, exercise level, body mass index, perceived body size, and ideal body size.Results. Weight management motive was positively predicted by body mass index in older males, and by perceived and ideal body size in older females. Other, more intrinsic, motives were negatively predicted by body mass index or perceived body size in older males or females. Such relationships were not significant in younger adolescents.Conclusion. Effects of body mass and body image on exercise motives emerge in adolescence, with gender differences. Such effects may influence exercise adherence and should be taken into account in exercise promotion programmes.     

Chronic stress and sex differences on the recall of fear conditioning and extinction

Chronic stress effects and sex differences were examined on conditioned fear extinction. Male and female Sprague–Dawley rats were chronically stressed by restraint (6 h/d/21 d), conditioned to tone and footshock, followed by extinction after 1 h and 24 h delays. Chronic stress impaired the recall of fear extinction in males, as evidenced by high freezing to tone after the 24 h delay despite exposure to the previous 1 h delay extinction trials, and this effect was not due to ceiling effects from overtraining during conditioning. In contrast, chronic stress attenuated the recall of fear conditioning acquisition in females, regardless of exposure to the 1 h extinction exposure. Since freezing to tone was reinstated following unsignalled footshocks, the deficit in the stressed rats reflected impaired recall rather than impaired consolidation. Sex differences in fear conditioning and extinction were observed in nonstressed controls as well, with control females resisting extinction to tone. Analysis of contextual freezing showed that all groups (control, stress, male, female) increased freezing immediately after the first tone extinction trial, demonstrating contextual discrimination. These findings show that chronic stress and sex interact to influence fear conditioning, with chronic stress impairing the recall of delayed fear extinction in males to implicate the medial prefrontal cortex, disrupting the recall of the fear conditioning acquisition in females to implicate the amygdala, and nonstressed controls exhibiting sex differences in fear conditioning and extinction, which may involve the amygdala and/or corticosterone levels.     

Sex differences in spatial and non-spatial Y-maze performance after chronic stress

Chronic restraint is known to alter hippocampal CA3 dendritic morphology and spatial memory in male rats. The present study examined whether female rats, which exhibit different anatomical adaptations to chronic stress than those of males, would also show spatial memory impairments. Male and female Sprague-Dawley rats were restrained for 6 h/day for 21 days, a time frame previously demonstrated to cause hippocampal CA3 dendritic atrophy. The day after the last restraint session, rats were tested on a Y-maze, a habituation task that can be used to assess spatial memory. Chronic stress impaired Y-maze performance in both sexes without affecting levels of locomotion as measured by total arm entries in the first minute. However, Y-maze performance of stressed females improved in 2-5 min when chronically stressed males continued to show poor Y-maze performance. The enhanced Y-maze performance of chronically stressed females occurred when total arm entries were higher compared to the entries made by males. Therefore, correlations were performed between total arm entries and spatial memory in 1 and 2-5 min. In the first minute when control females demonstrated functional spatial memory, female controls with the lowest locomotor levels exhibited the best performance. The correlations for stressed females were not significant, and neither were the correlations for any group in 2-5 min. Overall, these results show important sex differences in response to chronic stress with females exhibiting an ability to recover quickly from deficits in Y-maze performance.     

Socially induced renal pathology of captive wild rats (Rattus villosissimus)

Long-haired rats, Rattus villosissimus, were studied in large cages. Groups of adult rats (each of 3 males, or 1 male and 2 females) were observed during intermittent encounters with a male intruder for up to 9 days. Two further groups, each of 8 males and 8 females, were maintained for 70 days without introduction of intruders. Controls were kept in small cages in which intolerant behavior was rare. Behavior during attack resembled that of male R. norvegicus, but social relationships were less stable. Only observations on males are described in detail. Some rats collapsed under attack, though unwounded, and died when not removed. Collapse occurred sometimes after a few hours, but sometimes after many days of exposure. Exposure to attack was accompanied by a decline in body weight and by some adrenal hypertrophy. Two kinds of renal pathology are described: focal glomerular hypercellularity (FGH), probably due to glomerulonephritis, and dilated distal convoluted tubules. Neither condition occurred in the controls. FGH occurred in 3 of 12 rats (25%) that remained apparently healthy during the 9 days of continuous exposure, in 21 of 23 intruders (91%) that were exposed to intermittent attack over 9 days or less without becoming debilitated, and in 8 of 11 such rats (73%) that collapsed. All rats examined from 70-day colonies had FGH, whether collapsed or not. Dilated tubules occurred in 6 of 32 intruders (19%) exposed to intermittent attack, and in 2 of 6 animals that collapsed during 70 days of exposure. Renal pathology, especially glomerulonephritis, was therefore a correlate of social intolerance; but there was no evidence that it was a significant cause of death.     

Social factors influence haloperidol-induced catalepsy in rat

This study employed manipulations which presumably influence social interactions in rats: (1) paired housing with a heavier conspecific and (2) exposure to the odors of other rats. The dependent variable was the akinetic state induced by haloperidol, a neuroleptic and dopamine antagonist. In Experiment 1, adult male Long-Evans hooded rats were matched by weight and caged alone or in pairs with one rat 30 g heavier than its cagemate. All rats received haloperidol (1.5 mg/kg) and catalepsy testing. Heavy rats showed more catalepsy than the lighter member of pairs or weight-matched, singly housed controls. In Experiment 2, adult male rats were left unrecaged or were recaged into cages with bedding recently soiled by females or other adult males. After haloperidol (1.0 mg/kg), the rats exposed to bedding soiled by other adult males showed more catalepsy than did the control groups. Thus, the results of both experiments indicated that social factors can influence the akinesia induced by dopamine antagonists.     

Sex differences in maternal behaviors of immature rats: The role of emotionality

Immature rats are able to give maternal care to pups and may increase their inclusive fitness by helping newborn siblings. Immature males are generally reported to be more maternal than females. In this research we studied sex differences and the extent to which they may be due to a different emotional response to novelty. We studied maternal response in two groups of immature rats of both sexes: in the naive group, juveniles aged from 18 to 30 days were given one test and showed clear-cut sex differences. The experience group was submitted to repeated tests from 18 to 30 days of age, thus eliminating the effects of novelty: as a result, all differences between sexes disappeared. A second experiment was designed in 24-day-old females to differentiate the effects of repeated handling and exposure to the test situation from that of repeated exposure to pups; moreover, the effects of an anxiety-reducing drug (diazepam) were studied. Exposure to pups is particularly efficient in facilitating maternal response. Diazepam injection was also effective, but its control showed that the injection per se was responsible for the effect. In conclusion, our results stress the importance of response to novelty and suggest that sex differences in maternal behavior of immature rats may be modulated by different emotional responses by males and females. In fact, emotionality competes with, and may exert an inhibitory effect on, the expression of a vast array of behaviors. © 1994 Wiley-Liss, Inc.     

d-cycloserine reverses the detrimental effects of stress on learning in females and enhances retention in males

Exposure to acute, inescapable stress produces a facilitation of subsequent classical eyeblink conditioning in male rats. The same stress exposure produces a profound deficit in classical eyeblink conditioning in females. Activation of N-methyl-d-aspartate receptors (NMDAr) is necessary for the effect of stress on learning in males while the contribution of NMDAr activation to the deficit in learning after stress is unknown. Here, we tested the influence of d-cycloserine (DCS), a positive modulator of the NMDAr, in stressed or unstressed male and female rats. Groups of males and females were exposed to an acute stressful event. One day later, they began training with four sessions of trace eyeblink conditioning. Each day before training, they were injected with DCS (15 mg/kg) or saline. Females treated with DCS during training responded similarly to those that were untreated. However, those that were stressed and the next day treated with the drug during training did not express the typical learning deficit, i.e. they learned to time the CR very well. Because the drug was administered well after the stressor, these data indicate that DCS reversed the negative effects of stress on learning in females. In males, the effect of DCS was subtle, resulting in higher asymptotic responding, and enhanced retention in a drug-free retention test. Thus, as shown previously, training in the presence of an NMDA receptor agonist enhances associative learning and memory retention. In addition, it can reverse learning deficits that have already been induced.     

Effects of chronic ethanol consumption on gestation and lactation in rats

Chronic consumption of ethanol during pregnancy and lactation may lead to abnormalities in the fetus or infant. A group of female Wistar rats was submitted to ethanol treatment over a period of a month. A pair-fed control group received sucrose solution isocaloric to ethanol and the control group received water “ad libitum.” Afterward, the females were mated with males over a period of 20 days. At birth, each litter was maximized to eight pups and the remaining ones were decapitated to remove the fetal blood and brains. No significant difference was observed in fetal body and brain weight at birth. During lactation the ethanol and pair-fed groups gained less weight than the control group. After weaning, their weight became similar. Fetal blood glucose levels were decreased in the ethanol-treated group. One hundred percent of the pair-fed and control females delivered live fetuses at term and all survived; only 40% of the females in the ethanol group delivered, and one pup did not survive. Chronic ethanol treatment pointed to a possible reduction in the fertility. It seems likely that the change in body weight of ethanol-fed dams was caused by undernutrition.