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     

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 male pre-ejaculatory vocalizations on female receptive behavior in the rat (Rattus norvegicus)

Both male and female rats (Rattus norvegicus) emit ultrasounds during copulation. Bursts of ultrasounds from males that occur as ejaculation approaches are lower in frequency, longer in duration, and louder than those that appear earlier in the ejaculatory series. We attempted to determine if these pre-ejaculatory calls affect female sexual behavior. The behavior of females paired with devocalized males was compared with that of females paired with intact males, and in a second experiment tape-recorded vocalizations were played to females paired with devocalized males. Females were less receptive when paired with devocalized males; they were less likely to remain stationary when males attempted to mount. Playback of both types of calls restored female immobility toward control levels, although pre-ejaculatory calls were more effective than mating ones. Pre-ejaculatory calls restored running and training levels somewhat toward control level but to a lesser extent than female immobility.     

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.     

Receptivity of the female rat (Rattus norvegicus) after male devocalization: a ventral perspective

Male rats (Rattus norvegicus) emit at least two patterns of vocalization during copulation, the mating call and the pre-ejaculatory call. Both calls promote immobility of the female during lordosis, but the pre-ejaculatory calls are more effective. We undertook, through ventral observations of the mating pair, to determine if the female failed to assume or maintain the lordosis posture when mounted by a devocalized male and also to determine if the devocalized male was providing adequate stimulation to induce receptive behavior. Females were more likely to move away from the devocalized males before assuming the full lordosis posture. Furthermore, they were more likely to move away before the males had a chance to engage in intromissive behavior. However, when the females remained immobile long enough for the males to achieve a mount or intromission, there was little difference in the behavior of either animal that resulted from the devocalization of the male.     

Acute predator stress impairs the consolidation and retrieval of hippocampus-dependent memory in male and female rats

We have studied the effects of an acute predator stress experience on spatial learning and memory in adult male and female Sprague-Dawley rats. All rats were trained to learn the location of a hidden escape platform in the radial-arm water maze (RAWM), a hippocampus-dependent spatial memory task. In the control (non-stress) condition, female rats were superior to the males in the accuracy and consistency of their spatial memory performance tested over multiple days of training. In the stress condition, rats were exposed to the cat for 30 min immediately before or after learning, or before the 24-h memory test. Predator stress dramatically increased corticosterone levels in males and females, with females exhibiting greater baseline and stress-evoked responses than males. Despite these sex differences in the overall magnitudes of corticosterone levels, there were significant sex-independent correlations involving basal and stress-evoked corticosterone levels, and memory performance. Most importantly, predator stress impaired short-term memory, as well as processes involved in memory consolidation and retrieval, in male and female rats. Overall, we have found that an intense, ethologically relevant stressor produced a largely equivalent impairment of memory in male and female rats, and sex-independent corticosterone-memory correlations. These findings may provide insight into commonalities in how traumatic stress affects the brain and memory in men and women.     

Strain and gender specific effects in the forced swim test: effects of previous stress exposure

The chronic mild stress (CMS) procedure was developed in rodents to target anhedonia, the core symptom of depressive melancholia. Stress exposure has been shown to induce a variety of physiological, biochemical and behavioral alterations associated with depression, although its anhedonic consequences as indexed by either sucrose intake and preference or thresholds for brain stimulation reward are less reliably observed. In the present study, we assessed the effects of six weeks of CMS on the latter measure in two strains of male and female rats subsequently challenged with an acute psychophysical stressor, forced swimming; their behavior in the swimming cylinder was evaluated on two consecutive days. While brain stimulation reward thresholds and response rates were unchanged by CMS exposure, significant differences in forced swim behaviors were observed between male control and CMS groups. In particular, male Long Evans rats with a history of CMS showed the largest decrease in the duration of active behaviors on the second test day, a pattern less evident in the Sprague-Dawley strain of rats, or in any of the female groups. The results suggest that the effects of depressogenic manipulations are strain and gender dependent, with male Long Evans rats most susceptible, as demonstrated by the selective reduction of struggling behaviors. Inclusion of multiple measures, including the forced swim test, would provide a better understanding of the psychopathological profile engendered by chronic exposure to mild stressors and its genetic specificity.     

Relative contributions of the male and the female to sexual behavior and reproductive success in the Japanese quail (Coturnix japonica)

Two contrasting investigative techniques provided evidence consistent with the interpretation that female quail (Coturnix japonica) regulate male copulatory behavior by the duration of their immobility and through this behavioral mechanism they also control the rate of fertilization of their eggs. In Experiment 1, copulation tests with males and females from different genetic lines showed that the type of female that participated in a copulatory test significantly influenced the latency of the male's grab, mount, and cloacal contact responses and also determined the efficiency of the male's copulatory behavior. These measures of male performance were correlated with female immobility in Experiment 2, which used a more homogeneous population of quail. Furthermore, 2 of these measures (copulatory efficiency and the latency to make cloacal contact) were correlated with fertilization rate.     

Effects of Stress on Nonassociative Learning Processes in Male and Female Rats

In this study we assessed habituation and sensitization of the acoustic startle response (ASR) to discern whether intense, inescapable stress affects nonassociative learning differently in male and female rats. Rats were inescapably stressed 2 hours per day over 3 consecutive days. ASR magnitudes were measured at several times post-stress (1, 4, 8, and 15 days after cessation). Females generally showed greater ASR magnitudes (compared to males), but both sexes exhibited short and long-term habituation across the testing days. ASR magnitudes were only affected by stress in male subjects. The effect in males was an increase in short-term sensitization of the ASR on post-stress day-4. The results suggest that stressed males and females react differently to ASR testing, in that stress males appear to develop an exaggerated ASR response over repeated test sessions due to short-term sensitization. The source of the short-term sensitization is discussed with regards to possible stress-induced enhanced contextual learning during ASR testing on post-stress day-1.     

Pituitary-adrenal activity in acute and chronically stressed male and female mice lacking the 5-HT-3A receptor

The serotonin (5-HT)-3A receptor has been localized in limbic and brainstem structures that regulate hypothalamic--pituitary--adrenal (HPA) activity. We previously showed that 5-HT-3A receptor knock-out (KO) male mice displayed lower ACTH responses to acute restraint or lipopolysaccharide administration compared to age-matched wild-type (WT) males. In the present study, we found that pituitary-adrenal responses to acute stress were not different in female WT and KO mice. Furthermore, we examined the role of the 5-HT-3A receptor in regulation of chronic stress-induced HPA activity in both male and female WT and KO mice. The results show that ACTH, but not corticosterone, responses to novel restraint are lower in chronically cold stressed females compared to non-stressed control females but no effect of 5-HT-3A receptor deletion was observed. In contrast, male mice showed facilitated responses to novel restraint after chronic cold stress and this facilitation produced sex differences in ACTH responses to novel restraint between male and female chronically stressed KO mice. Together, these results indicate that there are sex differences in HPA responses to novel restraint in chronically stressed mice and these differences are partly related to 5-HT-3A receptor function.     

Gender Differences in Illusion Response: The Influence of Spatial Strategy and Sex Ratio

Two experiments explored factors related to gender differences in Ponzo illusion susceptibility. In Experiment 1, 54 male and 54 female (predominantly white, middle class) undergraduates were administered Witkin's Embedded Figures Test (EFT) and, on 2 separate occasions, a form of the Ponzo illusion. Results showed the Ponzo to be quite reliable over several days. Females were significantly more field dependent (as shown by slower responses to the EFT), and significantly more susceptible to the Ponzo illusion, than males. Furthermore, EFT performance correlated significantly with Ponzo susceptibility for females, but not for males, suggesting that the difference between males and females in Ponzo response may be due not to differences in field independence per se, but rather to differences in the strategies used to solve the illusion task. In Experiment 2, 111 male and 148 female (predominantly white, middle class) undergraduates were administered the Ponzo illusion twice, the 2 administrations separated by about 90 min. Again, the illusion task showed good reliability, and females were significantly more susceptible to the illusion. Furthermore, the magnitude of the difference between males and females was systematically related to the sex ratio (the ratio of the number of males to the number of females) of the particular session in which each subject happened to be participating. It is suggested that social factors such as sex ratio might affect the strategies participants use when doing illusion tasks, and perhaps other spatial skills tasks as well.     

Effects of stress on nonassociative learning processes in male and female rats

In this study we assessed habituation and sensitization of the acoustic startle response (ASR) to discern whether intense, inescapable stress affects nonassociative learning differently in male and female rats. Rats were inescapably stressed 2 hours per day over 3 consecutive days. ASR magnitudes were measured at several times post-stress (1, 4, 8, and 15 days after cessation). Females generally showed greater ASR magnitudes (compared to males), but both sexes exhibited short and long-term habituation across the testing days. ASR magnitudes were only affected by stress in male subjects. The effect in males was an increase in short-term sensitization of the ASR on post-stress day-4. The results suggest that stressed males and females react differently to ASR testing, in that stress males appear to develop an exaggerated ASR response over repeated test sessions due to short-term sensitization. The source of the short-term sensitization is discussed with regards to possible stress-induced enhanced contextual learning during ASR testing on post-stress day-1.     

Sensory cues that elicit ultrasonic vocalizations in female rats (Rattus norvegicus)

Female rats emit ultrasonic vocalizations during copulation. Female vocalizations are associated with darting and other proceptive behavior. In addition, females frequently call while approaching the male. A series of experiments was undertaken to determine whether female rats emit ultrasonic vocalizations in response to other rats or to their odors. Females were exposed either to bedding soiled by males or females or to devocalized conspecifics separated from the subject by a barrier. Females vocalized more to male cues than to female cues, regardless of whether the odor cues were from soiled bedding or from a devocalized conspecific. In addition, subjects vocalized more when presented with a devocalized female rather than a neutral stimulus. Furthermore, devocalized adult males, separated by a barrier, were more effective than either devocalized castrated or juvenile males in eliciting vocalizations; in turn, castrates and juveniles were more effective than neutral stimuli. Female calling was likely induced by odors from the male. In one experiment, the female subject was positioned in such a way that she could neither see or touch the stimulus male. Presentation of tape-recorded male vocalizations did not affect calling by the female. Vocalizations emitted by females in response to male odors may attract males or may facilitate subsequent copulatory behavior by the male.     

Permanent and transient effects of repeated preweaning stress on social and sexual behaviors of rats

We have reported that exposure of preweaning male and female rats to a model of unpredictable mild physical stressors (Neo-A) can decrease the behavioral and hormonal responses to acute and chronic stress as adults. In this paper we have analyzed the effect of Neo-A on development of social behaviors, including aggressiveness, social dominance, and sexual behavior in adulthood. The subjects were divided into two groups: Neo-A (daily exposed to unpredictable mild stresses- from day 2 up to day 15 of suckling; n = 30 litters) and controls (C) (undisturbed rats, except for testing, during the same period of life; n = 26 litters). When day 6 pups were submitted to a social clustering test the Neo-A group showed a higher rate of litter-mate clustering than C. The 35 days Neo-A males and Neo-A females submitted to a social behavior test after 24 h of social isolation also showed higher scores of time spent in active social interaction than controls, as well as a higher ratio of animals showing aggressive playing. A second social behavior test performed after 48 h of social isolation at days 75-80 of age revealed that only Neo-A females displayed increased social behavior and aggressive behaviors, whereas controls did not. A water competition test performed at 24 and 48 h after water deprivation showed that Neo-A adult males spent more time in possession of the drinking device and drank more frequently than C. When adult proestrous females were exposed to a sexual behavior test, the Neo-A group showed shorter latency and higher scores of lordosis quotient. These results support the view that exposure to this model of repeated mild stress early in life stimulates the development of social behavior, dominance and sexual behavior.     

Sexual experience and preference for males or females in the female rat

The influence of sexual experience on preference behavior was investigated in adult female rats. In the first experiment, preference behavior for sexually active males versus estrous females was investigated in female rats who were experienced with mounting behavior. Preference of these mount experienced females was compared to preference of females who were naive in this respect. Mount experience with estrous females induced a female-directed preference in ovariectomized female rats, irrespective of whether the females were treated with OIL or with testosterone-propionate (500 micrograms TP, injected once 48 h prior to testing). Sexually naive, OIL-treated females did not show a preference for males or females, but TP induced a preference for a male. Individual differences in mount frequency were not correlated with preference behavior. In the second experiment, the influence of experience with feminine sexual responses on preference behavior was investigated. OIL-treated and TP-treated females oriented equally toward males and females when they had been given the opportunity to copulate with males prior to the preference tests. The results strongly suggest that prior sexual experience is an important determinant of preference behavior. The female's behavior during sexual interactions was, however, not predictive of later preference.     

青少年应激下皮质醇应答与风险决策相关性的性别差异

本研究旨在探讨中国青少年应激下皮质醇应答和风险决策相关性的性别差异。本研究以健康初中生为被试者, 采用特里尔社会应激测试(Trier Social Stress Test, TSST)诱发机体应激反应, 测试唾液皮质醇在应激前后不同时间段的水平, 并要求被试者在应激状态下完成气球模拟风险决策任务(Balloon Analogue Risk Task, BART)。结果发现, 男性在TSST诱导下皮质醇反应度显著高于女性, 男性中高皮质醇应答者BART表现为更高程度的冒险行为和更低的总奖励金额, 而女性中高皮质醇应答者BART表现为更高的总奖励金额。研究结果提示,中国青少年应激条件下皮质醇应答与风险决策之间的联系存在性别差异, 尤其在男性, 高皮质醇应答者更具有冒险行为。     

Genotype modulates prenatal stress effects on aggression in male and female mice

Prenatal stress (heat and restraint) significantly increased postpartum aggression (proportion of animals fighting and/or the intensity of the behavior) in C57BL/6J female mice and reduced the behavior in DBA/2J females. For intermale aggression, prenatal stress increased the behavior (intensity of aggression) in C57BL/6J males but did not affect aggressive behavior in DBA/2J animals. Infanticidal behavior (the killing of young) exhibited by male mice was not influenced by prenatal stress in either strain. Relative anogenital distance measurements in neonates at birth did not serve as a reliable predictor of strain variation in prenatal stress effects. Prenatal stress did not influence this measure of prenatal androgen exposure in DBA/2J or C57BL/6J females. For males, prenatal stress elevated relative anogenital distance in C57BL/6J mice and decreased this measure in DBA/2J animals. Prenatal stress effects on aggressive behavior in male and female mice therefore depend upon genotype. Strain-dependent differences may be modulated by differences in endocrine reactivity to prenatal stress/and or differential central neural tissue sensitivity to hormones.     

Testosterone prevents synaptic loss in the perineal motoneuron pool in the spinal cord in male rats exposed to chronic stress

Chronic stress is known to induce disorders of reproductive neuroendocrine functions. Motoneurons of the spinal nucleus of the bulbocavernosus (SNB) in male rats play an important role in copulatory behavior. In the present study, it was examined whether chronic stress would alter synaptic organization of the SNB motoneurons and whether androgen would modify the changes under chronic stress. Five male rats were under restraint stress for 5 days per week for 3 weeks, and five males implanted subcutaneously with Silastic capsules containing testosterone were also exposed to stress. Five males served as unstressed controls. After 3 weeks of restraint stress, cholera toxin-horseradish peroxidase (CT-HRP) was injected into the bulbocavernosus muscles and animals were killed 2 days later. The spinal cords containing the SNB were dissected, processed with a modified tetramethylbenzidine (TMB) method for visualization of retrogradely transported CT-HRP, and examined ultrastructurally. Neuronal structures apposing the membranes of 150 SNB motoneurons (total for three groups) were analyzed by measuring the percentage of somatic membranes covered by synaptic contacts. The mean percentage of somatic membranes covered by synapses in males exposed to chronic stress was significantly less than that in controls or stressed males treated with testosterone. Size and number of synaptic contacts per unit length of somatic membranes in males exposed to stress were also significantly less than those in controls or stressed males treated with testosterone. There was no significant difference in any of the parameters between controls and stressed males treated with testosterone. Changes in plasma levels of testosterone showed the same profile as changes in the synaptic contacts. These results suggest that the SNB motoneurons of male rats exposed to chronic stress retain a considerable synaptic plasticity in response to androgen, and that androgen treatment can rescue the SNB system in male rats when under chronic restraint stress.     

Sex differences and estropausal phase effects on water maze performance in aged rats

An age-related decline in memory has been reported in male rats; however, there are few studies that have addressed these changes in aged female rats. In young female rats, hormonal cycles influence behavior. By the age of 22 months most female rats have not had regular hormonal cycles for at least 9 months. In the current study we examined how the hormonal status (persistent estrus and pseudo-pregnant) of the aged (22-24 months) female rat (Long Evans) influenced performance on a spatial version of the Morris water maze and compared this to aged male rats. Aged females in persistent estrus showed better performance on the water maze than both aged females that were pseudopregnant and aged males. Thus, postestropausal hormonal status may influence the course of aging in females.     

CNTF对应激大鼠行为障碍和海马CA1神经元损害的作用

实验采用 ｏｐｅｎ ｆｉｅｌｄ测定、 Ｎｉｓｓｌ染色、 Ｂｉｅｌｓｃｈｏｗｓｋｙ－Ｇｒｏｓ－Ｌａｗｒｅｎｔｊｅｗ染色和常规透射电镜技术,观察急性和慢性足底电击应激大鼠的ｏｐｅｎ ｆｉｅｌｄ行为和海马ＣＡ１神经元形态的变化,及双侧海马注射睫状神经营养因子（ＣＮＴＦ）对它的影响。结果表明,急性应激大鼠ｏｐｅｎ ｆｉｅｌｄ行为活动增加,海马ＣＡ１神经元形态无明显变化;慢性应激大鼠ｏｐｅｎ ｆｉｅｌｄ行为活动减少,海马ＣＡ１神经元出现明显的损伤性形态变化;睫状神经营养因子对对照组大鼠和急性应激大鼠的ｏｐｅｎ ｆｉｅｌｄ行为和海马ＣＡ１神经元形态均无明显作用,但可显著减轻慢性应激大鼠海马ＣＡ１神经元损伤程度,改善其行为障碍。实验结果提示睫状神经营养因子可能通过保护海马神经元从而改善慢性应激大鼠的行为障碍。