Effects of chronic social stress during lactation on maternal behavior and growth in rats

Maternal mood disorders such as depression and chronic anxiety can negatively affect the lives of not only mothers, but also of partners, offspring, and future generations. Chronic exposure to psychosocial stress is common in postpartum mothers, and one of the strongest predictors of postpartum depression is social conflict. The objective of the current study was to evaluate the effects of chronic social stress (CSS) during lactation on the maternal behavior (which consists of maternal care and aggression toward a novel conspecific) of lactating rats, as well as on the growth of the dams and their offspring. It was hypothesized that chronic daily exposure to a novel male intruder would alter the display of maternal behavior and impair growth in both the dam and offspring during lactation due to the potentially disruptive effects on maternal behavior and/or lactation. The data indicate that CSS during lactation attenuates maternal care and the growth of both dams and pups, and increases self-grooming and maternal aggression toward a novel male intruder. These results support the use of CSS as a relevant model for disorders that impair maternal behavior and attenuate growth of the offspring, such as postpartum depression and anxiety.     

母性应激对母性行为和心理功能的影响

成为母亲对女性而言是人生经历的特殊阶段, 她们在这个阶段发生的生理和心理的适应性改变对其自身和子代健康具有重要意义。母性应激是阻碍母亲适应性改变顺利进行的重要因素。母性应激会破坏人类母亲和雌性哺乳动物的母性行为、认知功能和情绪调节, 这种影响与糖皮质激素、催产素、催乳素等内分泌系统的调节失常; 母性环路、边缘系统及前额叶皮质等神经环路对刺激的神经反应改变以及神经发生、树突和突触重塑的可塑性变化有关。     

Perioral anesthesia disrupts maternal behavior during early lactation in Long-Evans rats

The role of perioral somatosensory stimulation from pups in maternal behavior was investigated in lactating Long-Evans rats (Rattus norvegicus) during early lactation by local anesthesia of the mystacial pads with lidocaine, which blocks conduction in the infraorbital nerve. It was concluded that (1) acute perioral anesthesia markedly inhibited pup retrieval when the subjects had no formal pretreatment retrieval experience. Further, these dams displayed little tolerance to the lidocaine treatment when they were tested repeatedly. (2) The severity of the effects of perioral anesthesia on retrieval was dependent upon prior experience and the testing situation. Following pretreatment retrieval experience, and in a test cage with dark and light compartments which provided a strong incentive to retrieve, 80% of lidocaine-injected dams did retrieve. However, retrieval efficiency was impaired by perioral anesthesia, largely due to increased time in contact with pups prior to each retrieval and to increased carrying time. (3) Perioral anesthesia also inhibited pup licking, but not self-grooming, suggesting that the former, but not the latter, is largely under peripheral stimulus control and that deficits in maternal oral activities cannot be due to impairment of mouth opening and use. (4) The onset of nursing behavior was delayed until after the recovery of snout sensations and retrieval. This suggests that a maternal behavior not directly involving the mouth is nonetheless dependent upon the dam's receipt of perioral tactile input from pups.     

Effects of septal-forebrain lesions on maternal aggression and maternal care

Septal-forebrain lesions significantly increased the defensive reactions of lactating Long-Evans rats (n = 13) relative to nonlesioned control females. The lesions greatly enhanced defensive behaviors on a number of standard tests (e.g., responsiveness to humans and anesthetized conspecifics) while abolishing aggression toward intruding male conspecifics. The lesions also produced a striking disruption in maternal behavior as evidenced by absence of nest building, reduced litter weights, failure to retrieve, lick, or nurse pups, and increased cannibalization. While these results cannot be interpreted as indicating that maternal aggression is equivalent to offense, they are congruent with such a view. Certainly they are not supportive of a view that maternal aggression is primarily defensive. The lesion-induced abolition of maternal attack may have resulted from an inhibition of offensive tendencies by heightened defensiveness and/or reduced pup stimulation. There was no evidence that the lesion-induced impairment in maternal behavior resulted from a failure to sequence the individual behavioral acts comprising maternal behavior. Rather, all features of maternal care seemed to be greatly attenuated.     

Effects of acute restraint stress on set-shifting and reversal learning in male rats

Exposure to acute stress alters cognition; however, few studies have examined the effects of acute stress on executive functions such as behavioral flexibility. The goal of the present experiments was to determine the effects of acute periods of stress on two distinct forms of behavioral flexibility: set-shifting and reversal learning. Male Sprague-Dawley rats were trained and tested in an operant-chamber-based task. Some of the rats were exposed to acute restraint stress (30 min) immediately before either the set-shifting test day or the reversal learning test day. Acute stress had no effect on set-shifting, but it significantly facilitated reversal learning, as assessed by both trials to criterion and total errors. In a second experiment, the roles of glucocorticoid (GR) and mineralocorticoid receptors (MR) in the acute-stress-induced facilitation of reversal learning were examined. Systemic administration of the GR-selective antagonist RU38486 (10 mg/kg) or the MR-selective antagonist spironolactone (50 mg/kg) 30 min prior to acute stress failed to block the facilitation on reversal learning. The present results demonstrate a dissociable effect of acute stress on set-shifting and reversal learning and suggest that the facilitation of reversal learning by acute stress may be mediated by factors other than corticosterone.     

The offensive nature of maternal aggression in mice: Effects of fluprazine hydrochloride

The phenylpiperazine fluprazine hydrochloride was used to test the hypothesis that maternal aggression in laboratory mice reflects offensive motivation. Lactating females (n = 8 per condition) tested for aggression following drug treatment (1.0 mg/kg and 5.0 mg/kg of fluprasine) were significantly less aggressive than saline controls according to all measures used. The findings support the hypothesis that maternal aggression is offensive in nature, and provide no evidence that maternal attack is a mixture of offensive and defensive tendencies.     

Effect of conspecific sex on aggression during pregnancy and lactation in golden hamsters

The effect of conspecific sex on maternal aggression in hamsters was determined by comparing the frequency of aggressive responses by dams continuously housed with either a virgin male or female cagemate during pregnancy and lactation. Dams easily established aggressive dominance over male cagemates soon after pairing, and their aggression was low thereafter for the duration of pregnancy and lactation. The aggression of dams with females, on the other hand, tended to fluctuate with highs during mid pregnancy and mid lactation and lows around birth. When dam aggression was low around birth, female cagemates frequently became aggressively dominant, and several dams lost their litters. The higher aggression of dams toward females than males is probably a reflection of greater intrasexual competition for environmental resources that includes pups.     

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.     

The potential effects of protected nests and cage complexity on maternal aggression in house mice

I studied the behavior of nursing house mice (Mus musculus) in captivity and used a two-by-two factorial design to test the hypothesis that the combination of a protected nest along with a chance for the intruders to retreat would improve the ability of resident females to defend their litters from infanticidal males. A chance for the intruder to retreat was manipulated by testing the resident females in either a single- or a two-compartment cage. The effect of a protected nest was examined by providing females with a nest box having a narrow entrance. During each test, an infanticidal adult male was introduced into the cage of a resident female and her pups. I observed that neither the presence of a protected nest nor the chance for the intruders to retreat to a different compartment, or a combination of the two, increased the ability of a female to defend her litter against an intruder male. Moreover, neither of these two factors influenced the overall behavior of the resident females. I obtained similar results after using data from previous studies to examine the influence of both of these factors on the efficiency of maternal aggression. Overall, these two approaches showed that females are often unable to prevent intruders from committing infanticide. I discuss the validity of the hypothesis that maternal aggression evolved as a mechanism to protect offspring from infanticide. Aggr. Behav. 24:385–396, 1998. © 1998 Wiley-Liss, Inc.     

Effects of daily stress on negative mood

This article examines the influence of daily stressors on mental health in a community sample. Ss were 166 married couples who completed diaries each day for 6 weeks. In pooled within-person analyses, daily stressors explained up to 20% of the variance in mood. Interpersonal conflicts were by far the most distressing events. Furthermore, when stressors occurred on a series of days, emotional habituation occurred by the second day for almost all events except interpersonal conflicts. Contrary to certain theoretical accounts, multiple stressors on the same day did not exacerbate one another's effects: rather an emotional plateau occurred. Finally on days following a stressful event, mood was better than it would have been if the stressor had not happened. These results reveal the complex emotional effects of daily stressors, and in particular they suggest that future investigations should focus primarily on interpersonal conflicts.     

Infanticide and maternal aggression: Synchrony of male and female reproductive strategies in mice

Thirty-six percent of male mice from three strains attacked newborn pups sired by another male. No male attacked its own offspring. Females did not show differential aggression toward males likely (strangers) or unlikely (sires) to attack their pups. Both forms of aggression were unaffected by housing in rooms which did or did not contain the aggression targets. The three strains differed in strength of maternal aggression but not in the incidence of infanticide. Females showed more aggression when mated with males of the same, rather than a different, strain but no differences with intruders of the same or a different strain. Infanticide by males is best viewed as a postcopulatory, intermale-competition strategy, and maternal aggression as a counter strategy.     

Effects of serotonin receptor agonists and antagonists on offensive aggression in mice

The effects of serotonin receptor agonists 5-methoxytryptamine and quipazine, and antagonist mianserin on resident-intruder offensive aggression were investigated. Both agonists reduced aggression. The fact that 5-methoxytryptamine preferentially binds to 5-HT-1 receptors strongly suggest that the decreased aggression with S-methoxytryptamine was related to stimulation of an inhibitory 5-HT-1 receptor. It is also suggested that the reduction in aggression with quipazine was related to quipazine's preferential binding to the 5-HT-1 receptor. The 5-HT-2 receptor antagonist mianserin reduced aggression suggesting that 5-HT-2 receptor blockade is inhibitory for aggression. Thus, two serotonin classes of receptors may be differentially involved in offensive aggression.     

Chronic restraint stress impairs T-cell immunity and promotes tumor progression in mice

Long-term exposure to stressful situations can affect the immune system. The T-cell response is an important component of anti-tumoral immunity. Hence, impairment of the immune function induced by a chronic stressor has been postulated to alter the immunosurveillance of tumors, thus leading to a worse neoplastic prognosis. Here, we show that chronic restraint stress affects T-cell mediated immunity in mice. This was evidenced by a decrease of mitogen-induced T-cell proliferation, a reduction in CD4(+)T lymphocyte number and a decrease of tumor necrosis factor-alpha (TNF-alpha) and Interferon-gamma (IFN-gamma) production in stressed mice. Additionally, mice subjected to chronic restraint stress displayed an enhancement of tumor growth in a syngeneic lymphoma model, i.e. an increase of tumor proliferation and a reduction of animal survival. Finally, stressed mice had a reduced specific cytotoxic response against these tumor cells. These results suggest that chronic exposure to stress promotes cancer establishment and subsequent progression, probably by depressing T-cell mediated immunity. The T-cell immunity impairment as well as the tumor progression enhancement emphasize the importance of the therapeutic management of stress to improve the prognosis of cancer patients.     

Pain‐induced aggression and changes in social behavior in mice

The effects of neuropathic, formalin, and acetic acid‐induced visceral pain were investigated on the social and aggressive behaviors in the Swiss male mice. Neuropathic pain was induced by tibial nerve transection (TNT). Also, somatic and visceral pain was conducted by intraplantar injection of diluted formalin (1%, 20 μl) and intraperitoneal administration of acetic acid (0.6%, 200 μl), respectively. Fourteen and twenty one days after the TNT surgery, and also, 1 and 7 days following formalin and acetic acid administration, the three‐chambered test was used to determine sociability and preference for social novelty and resident/intruder test was used for the evaluation of the aggressive behaviors. In the sociability phase of the three‐chambered test, all the three models of pain did not change the animal's sociability. However, in the social novelty preference phase, the animals in pain showed deficits in social novelty preference by a significant increase in the time spent with the familiar mice compared to the control groups. Also, animals in pain significantly showed more aggressive behaviors like biting and clinching and have much less attack latency in comparison to the control groups. Pain‐induced changes in the social novelty preference and aggressive behaviors continued in the neuropathic group until the end of the experiment. However, 7 days following the induction of both formalin and visceral pain, animals' social memory, and aggression almost returned to the standard value. These results suggest that long‐lasting pain could lead to social memory impairment and increase aggressive behaviors in mice.     

Relationship between maternal aggression and maternal care in the rat

Aggression among female rats is almost entirely confined to the period of late pregnancy and lactation. Behaviorally it is similar to the aggression of males including piloerection and lateral attacks, but it differs in its function. Unlike male aggression which serves to establish a social hierarchy and a territory, i. e., is competitive, maternal aggression is protective, i. e., it serves to prevent predation of the mother's offspring. In this respect it is closely related temporally and causally to maternal care; if the offspring are removed maternal aggression wanes almost immediately–its function no longer exists! Studies on aggression by mothers, among rats, from the author's laboratory are reviewed and comparisons made with maternal care. As noted, maternal aggression and maternal care are closely related during the cycle of maternal behavior and they share a similar hormonal basis and possibly the effect of uterine stimulation, but maternal care requires prolactin and the decline of progesterone while maternal aggression appears independent of pituitary hormones and does not require a decline in progesterone. Maternal aggression like maternal care appears to be organized into a hormonal phase, during pregnancy, parturition, and for about a week postpartum and a nonhormonal phase thereafter. Bilateral radiofrequency lesions of the lateral midbrain peripeduncular nucleus (PPN) produce deficits in maternal aggression if made on lactation day 7 (L7), but not earlier, without producing significant deficits in maternal behavior. Experiments showed that the PPN does not mediate hormonally stimulated maternal aggression; it appears to mediate only nonhormonally stimulated maternal aggression. Studies on the role of pregnancy hormones on long-term retention of maternal aggression and the role of olfaction in maternal aggression are also reviewed. © 1994 Wiley-Liss, Inc.     

Prenatal maternal stress: Differential effects upon male and female offspring responses to restraint stress as adults

Pregnant primiparous rats were subjected to four days of light restraint stress on postconception days 7 through 10, inclusive, coincident with the development of the fetal gastrointestinal system. Twenty male and twenty female offspring from prenatally stressed and nonstressed rats were then subjected to two hours of supine cold-restraint as adults. Eighty percent of nonprenatally stressed offspring developed gastric lesions, while 47.5% of offspring of prenatally stressed mothers displayed lesions. A significant sex-stress interaction was detected, indicating that male offspring from prenatally stressed mothers display less severe gastric lesions in response to restraint stress as adults than do male offspring from nonprenatally stressed mothers. Female offspring from both prenatal stress conditions showed similar levels of stress-induced lesions.     

Effects of stress on defensive aggression and dominance in a water competition test

Water-deprived rats in a pair competing for a single source of water quickly establish a firm relationship during which one rat drinks consistently more (dominant) than the other (submissive) animal. This relationship is formed during the first competition and is very stable during subsequent tests. Exposure of dominant rats to a severe (18 hrs immobilization), but not a mild (2 hrs immobilization), stressor reduced markedly aggressive behavior and inverted transiently the dominant submissive relationship of the pairs. Exposure of submissive rats to the severe stressor resulted in only minor reductions of aggressive behavior in these animals. Prestress anxiety predicted stress effects in the dominant animals in that high-anxious animals lost more dominant behavior and weight during stress as compared with low-anxious rats. Thus, severe stress can transiently reduce dominant but not submissive behavior during water competition and high-anxious rats are more prone to lose their aggressive behavior.