Testosterone propionate inhibits maternal aggression in mice

Daily injections of testosterone propionate (TP) significantly decreased the number of attacks exhibited by lactating female mice toward male intruders. Treatment with TP also depressed the body weights of the dams as well as their lactation performance but these effects were observed long after deficits in aggression were noted. The results are discussed in terms of a direct effect of the steroid on central neural tissue mediating the behavior.     

Prenatal stress alters maternal aggression in mice

Prenatal stress (heat and restraint) reduced pregnancy-induced and elevated postpartum aggression in Rockland-Swiss (R-S) albino female mice. Though prenatally-stressed females were indistinguishable from control animals with respect to parental behavior during the virgin state, the former displayed slightly lower levels of nestbuilding during early pregnancy, and delivered slightly more male offspring at parturition. The young born to prenatally-stressed females exhibited deficits in birth weights and body weight gain in contrast to pups delivered by control females. The anogenital distances of prenatally-stressed females were shorter than those of control females, suggesting that alterations in fetal testosterone exposure may be responsible for disruptions in behavior and reproduction.     

Prenatal testosterone exposure elevates maternal aggression in mice

Pregnant Rockland-Swiss (R-S) female mice were injected with oil, 0.5, 1.0 or 2.0 micrograms of testosterone propionate (TP) on days 12, 14 and 16 of gestation and the maternal aggressive behavior of their resulting female offspring was examined in adulthood. Prenatal exposure to 1 or 2 micrograms of TP, but not 0.5 micrograms of the steroid, significantly increased the number of attacks displayed by parturient mice toward adult male intruders. The behavioral effects on aggression were observed in the absence of effects on external morphology, body weight, or lactational performance. The findings support previous research showing that the development of feminine behavior may be sensitive to prenatal androgens. The possibility that the presence of fetal testosterone augments both male and female aggressive behavior is discussed.     

Prenatal stress reduces maternal aggression by mice offspring

Pregnant mice were subjected to the simultaneous stress of heat, restraint and bright lights during the last trimester of gestation whereas control mothers remained unhandled in the home cage. As adults, prenatally-stressed and nonstressed mice were mated and tested for maternal aggression. Compared with nonstressed controls, prenatally-stressed females bit intruder males on significantly fewer occasions. Prenatal stress therefore reduced maternal aggression by mice offspring. Prenatal stress also significantly reduced maternal and neonatal body weight. Because the appearance of maternal aggression characteristically has been associated with the postpartum period, prenatal stress may reduce maternal aggression in mice by disrupting gonadotropin secretions (possibly prolactin) associated with the lactational phase.     

Some situational and experiential determinants of maternal aggression in mice

Five experiments were conducted in order to examine the influence of some simple situational and experiential factors on the maternal aggression displayed by Rockland-Swiss (R-S) Albino mice toward adult male R-S intruders. The results of Experiment 1 showed that aggression is highest during the early lactation period (Postpartum Days 4 and 8) and is absent by the end of the lactation period (Postpartum Days 16 and 20). Experiment 2 showed that the aggression displayed by recently parturient (i.e., early lactating) females rapidly declines during a 10 minute test session with most attacks exhibited during the first 3 minutes of the encounter and few thereafter. The results of Experiment 3 showed that the behavior is significantly reduced when aggression testing takes place in a neutral cage as compared to testing in the homecage environment. The findings of Experiment 4 showed that young male and female intruders (25 and 45 days of age) are attacked as vigorously as adult (65 days of age) intruders of both sexes. The results of Experiment 5 showed that postweaning social deprivation (i.e., isolation) does not influence the development of aggression by lactating females. The significance of these findings for our understanding of the psychobiological basis of maternal aggression and other forms of agonistic behavior is discussed.     

A longitudinal analysis of maternal aggression in Rockland-Swiss albino mice

Female Rockland-Swiss albino mice were tested for aggression during 6 successive pregnancies and lactation periods or until they ceased to re-mate. Fighting behavior was limited only to the lactation phase of each reproductive cycle. Although most animals exhibited fighting during every lactation period they completed, some exhibited fighting in some lactation periods but not in others. The intensity of aggression, as measured by the time spent fighting, was highest during the beginning of each lactation period and declined by the end of each period. Moreover, the intensity of aggression increased across the first 3 lactation periods and then declined on later lactation periods to a point below initial levels. Finally, the fighting behavior exhibited by multiparous animals was not due simply to previous fighting experience in that some multiparous mice exhibited postpartum aggression on the 6th lactation period in the absence of fighting experience during earlier lactation periods.     

促肾上腺皮质激素释放因子及其受体的研究

促肾上腺皮质激素释放因子（corticotropin-releasing factor,CRF）是一种与应激密切相关的神经内分泌肽,通过与G蛋白偶联的2种受体结合发挥整合、协调内分泌、自主神经系统、免疫系统及行为学各方面对应激的反应。     

Neurotensin inversely modulates maternal aggression

Neurotensin (NT) is a versatile neuropeptide involved in analgesia, hypothermia, and schizophrenia. Although NT is released from and acts upon brain regions involved in social behaviors, it has not been linked to a social behavior. We previously selected mice for high maternal aggression (maternal defense), an important social behavior that protects offspring, and found significantly lower NT expression in the CNS of highly protective females. Our current study directly tested NT's role in maternal defense. Intracerebroventricular (i.c.v.) injections of NT significantly impaired defense in terms of time aggressive and number of attacks at all doses tested (0.05, 0.1, 1.0, and 3.0 μg). Other maternal behaviors, including pup retrieval, were unaltered following NT injections (0.05 μg) relative to vehicle, suggesting specificity of NT action on defense. Further, i.c.v. injections of the NT receptor 1 (NT1) antagonist, SR 48692 (30 μg), significantly elevated maternal aggression in terms of time aggressive and attack number. To understand where NT may regulate aggression, we examined Fos following injection of either 0.1 μg NT or vehicle. Thirteen of 26 brain regions examined exhibited significant Fos increases with NT, including regions expressing NT1 and previously implicated in maternal aggression, such as lateral septum, bed nucleus of stria terminalis, paraventricular nucleus, and central amygdala. Together, our results indicate that NT inversely regulates maternal aggression and provide the first direct evidence that lowering of NT signaling can be a mechanism for maternal aggression. To our knowledge, this is the first study to directly link NT to a social behavior.     

Studies on wild house mice. VII. Prenatal maternal environment and aggression

The effect of the maternal environment on intermale aggression was studied by means of embryo transfer of genetically selected aggressive (SAL) and nonaggressive wild house mice (LAL), and their reciprocal F₁'s, to standard (NMRI) females. No effect was found on the attack latency scores (ALS), i.e., aggression: all genotypes born and raised under natural conditions showed an ALS similar that of genotypes born and raised by NMRI females. Since previous studies on wild house mice failed to demonstrate postnatal effects on aggression, and the present results indicate the absence of prenatal maternal environmental effects on aggression, the primacy of genetic over maternal variance in the development of adult intermale aggression in wild house mice is indicated.     

促肾上腺皮质激素释放因子与肠易激综合征

肠易激综合征(IBS)是一种个体特异性、多病因的异质性疾病,其发病和患者的精神状态、社会环境、生活应激等多种心理社会因素密切相关。促肾上腺皮质激素释放因子(CRF)是一种介导下丘脑-垂体-肾上腺(HPA)轴对应激反应的关键调节肽,参与脑-肠轴互动,通过影响胃肠道动力、内脏高敏感和肠道感染等参与IBS的发病。     

Corticotropin-releasing hormone promotes blastocyst implantation and early maternal tolerance

The semi-allograft embryo in the blastocyst stage implants itself in the endometrium, yet no immune rejection processes are activated. Embryonic trophoblast and maternal decidua produce corticotropin-releasing hormone (CRH) and express Fas ligand (FasL), a proapoptotic cytokine. We found that antalarmin, a CRH receptor type 1 antagonist, decreased FasL expression and promoted apoptosis of activated T lymphocytes, an effect which was potentiated by CRH and inhibited by antalarmin. Female rats treated with antalarmin showed a marked decrease in implantation sites and live embryos and diminished endometrial FasL expression. Embryos from mothers that lacked T cells or from syngeneic matings were not rejected when the mothers were given antalarmin. These findings suggested that locally produced CRH promotes implantation and maintenance of early pregnancy primarily by killing activated T cells.     

Deletion of corticotropin-releasing factor binding protein selectively impairs maternal, but not intermale aggression

Corticotropin-releasing factor (CRF) binding protein (CRF-BP) is a secreted protein that acts to bind and limit the activity of the neuropeptides, CRF and urocortin (Ucn) 1. We previously selected for high maternal defense (protection of offspring) in mice and found CRF-BP to be elevated in the CNS of selected mice. We also previously determined that both CRF and Ucn 1 are potent inhibitors of offspring protection when administered centrally. Thus, elevated CRF-BP could promote defense by limiting endogenous actions of CRF or Ucn 1. To test this hypothesis, we crossed the deletion for CRF-BP into the mice selected for high maternal defense and evaluated offspring protection and other maternal behaviors. CRF-BP knockout (KO) mice exhibited significant deficits in maternal aggression relative to wild-type (WT) mice in three different measures. Other maternal features were almost identical between groups, including dam and pup weight, litter size, nursing time, and pup retrieval. Both groups performed similarly in a forced swim stress test and aggression in both groups was reduced following the swim test. Virgin KO female mice exhibited higher levels of anxiety-like behavior in terms of decreased time in the light portion of the light/dark box test. For males, no differences in light/dark box or swim test were found. However, increased anxiety-like behavior in male KO mice was identified in terms of contact and approach to a novel object both with and without previous exposure to the swim test. No differences in isolation induced resident intruder male aggression were found between groups. Together, these results indicate that loss of CRF-BP selectively impairs maternal, but not intermale aggression and that loss of the gene induces anxiety-like behavior in males and females, but there are sex differences in terms of how that anxiety is revealed.     

Medial hypothalamic involvement in maternal aggression of rats

Extensive electrolytic lesions of the medial hypothalamus, or more restricted ones in its ventral division, decreased maternal aggression in rats operated upon on postpartum Days 2 and 3 and tested with female intruders 4 days later. Maternal aggression was attenuated also in mothers receiving intrahypothalamic infusions with ibotenic acid or parasagittal knife cuts along the lateral border of the ventromedial hypothalamic nucleus; in addition, the females with ibotenate lesions or knife cuts showed impaired lordosis behavior. None of the hypothalamic interventions were associated with deficits in pup retrieval. Lactation was impaired in groups with hypothalamic electrocoagulations but not in mothers with ibotenate lesions or knife cuts. The results suggest that the ventromedial hypothalamus and its lateral connections participate in control of maternal aggression.     

Corticotropin-releasing factor modulates defensive-withdrawal and exploratory behavior in rats

The role of corticotropin-releasing factor (CRF), an endogenous neuropeptide, in modulating species-typical responses was examined in an unfamiliar open field containing a small chamber. Rats placed in this small chamber spent most of their time withdrawn in it. However, rats given an intracerebroventricular injection (20 micrograms) of alpha-helical CRF(9-41), a CRF receptor antagonist, emerged from the chamber and explored the unfamiliar open field. Additional studies showed that after 1 exposure to the test environment, vehicle-treated rats increased their time spent in the open field and returned intermittently to the chamber. This result suggests that reexposure reduces the threatening impact of an unfamiliar open field. Importantly, CRF (300 ng) injected centrally, but not peripherally, before reexposure to the test environment significantly reduced exploration in the open field and increased a pattern of defensive-withdrawal into the chamber. Data suggest that whether defensive-withdrawal or exploratory behavior is exhibited may depend on CRF actions in brain systems that mediate the perception of threat in the environment.     

Aggressive experience and maternal aggression in the Mongolian gerbil

Some recent reports suggest that female rodents which have experienced frequent aggressive encounters during lactation maintain higher levels of aggression than non-lactating controls, even after their pups are weaned. To test whether aggressive experience during lactation produced a different effect from aggressive experience at other times, three groups of female gerbils each were observed during 10 exposures to unfamiliar male intruders over a 5 week period. During week 1, lactating females were more aggressive than virginal controls. During the remaining weeks, neither lactating nor weaned females were significantly more aggressive than controls. It was concluded that the effects of repeated aggressive experience are similar whether the females are lactating or not.     

Predatory aggression in male mice selectively bred for isolation-induced intermale aggression

Male mice differing in their genetically determined disposition for isolation-induced intermale aggression were compared on behaviors related to predatory aggression. An ongoing sequence of selective breeding established high-aggressive (Turku Aggressive: TA) and low-aggressive (Turku Non-Aggressive: TNA) lines from an outbred Swiss albino foundation stock. The parental strain, designated the Normal (N) strain, has been kept as a control line and is bred without regard to aggressiveness. Testing consisted of dropping a live cricket into the home cage of the individually housed experimental mice. Results showed that the TA males displayed shorter latencies to attack and spent more time in chasing, attacking, and consuming crickets than did TNA and N males. The TNA males displayed significantly less predatory aggression than both the TA and N males. When brothers of the males tested for predatory aggression were tested for intermale aggression, a similarly significant effect of breeding line was obtained for the latency to attack. Testing consisted of placing an intact male mouse into the cage of the male to be tested. The results suggest that there may be parallels in genetic variation between intermale and predatory attacking.     

Prenatal stress reduces intermale aggression in mice

Prenatal stress (heat and restraint) significantly reduced intermale aggression (percentage of animals fighting and the number of attacks and lunges) in Rockland-Swiss Albino mice. These data, in combination with previous reports showing deficits in male copulatory responses, suggest that a wide array of androgen-dependent social behaviors may be influenced by prenatal stress.     

Studies on wild house mice (VIII): Postnatal maternal influences on intermale aggression in reciprocal F1's

Previous findings have shown a difference in attack latencies, i.e., aggression, between reciprocal F₁'s of a line selected for short attack latency (SAL) and a line selected for long attack latency (LAL). In the present study, we investigated the influence of postnatal maternal environment on attack latency scores (ALSs). The results show that only the evolution of the ALSs over 3 consecutive days is influenced by crossforstering. Accordingly, we conclude that the postnatal maternal environmental affects ALSs only to a small extent.