Estrogen receptor-alpha mediates estrogen protection from angiotensin II-induced hypertension in conscious female mice

It has been shown that the female sex hormones have a protective role in the development of angiotensin II (ANG II)-induced hypertension. The present study tested the hypotheses that 1) the estrogen receptor-alpha (ERalpha) is involved in the protective effects of estrogen against ANG II-induced hypertension and 2) central ERs are involved. Blood pressure (BP) was measured in female mice with the use of telemetry implants. ANG II (800 ng.kg(-1).min(-1)) was administered subcutaneously via an osmotic pump. Baseline BP in the intact, ovariectomized (OVX) wild-type (WT) and ERalpha knockout (ERalphaKO) mice was similar; however, the increase in BP induced by ANG II was greater in OVX WT (23.0 +/- 1.0 mmHg) and ERalphaKO mice (23.8 +/- 2.5 mmHg) than in intact WT mice (10.1 +/- 4.5 mmHg). In OVX WT mice, central infusion of 17beta-estradiol (E(2); 30 microg.kg(-1).day(-1)) attenuated the pressor effect of ANG II (7.0 +/- 0.4 mmHg), and this protective effect of E(2) was prevented by coadministration of ICI-182,780 (ICI; 1.5 microg.kg(-1).day(-1), 18.8 +/- 1.5 mmHg), a nonselective ER antagonist. Furthermore, central, but not peripheral, infusions of ICI augmented the pressor effects of ANG II in intact WT mice (17.8 +/- 4.2 mmHg). In contrast, the pressor effect of ANG II was unchanged in either central E(2)-treated OVX ERalphaKO mice (19.0 +/- 1.1 mmHg) or central ICI-treated intact ERalphaKO mice (19.6 +/- 1.6 mmHg). Lastly, ganglionic blockade on day 7 after ANG II infusions resulted in a greater reduction in BP in OVX WT, central ER antagonist-treated intact WT, central E(2) + ICI-treated OVX WT, ERalphaKO, and central E(2)- or ICI-treated ERalphaKO mice compared with that in intact WT mice given just ANG II. Together, these data indicate that ERalpha, especially central expression of the ER, mediates the protective effects of estrogen against ANG II-induced hypertension.     

Different effects of subchronic doses of 17-beta estradiol in two ethologically based models of anxiety utilizing female rats

Estrogen may have differing effects on 'anxiety' responses under different conditions. The current study tested the effects of estrogen on anxiety-like behavior when administered for 6-7 days in ovariectomized (OVX) female rats. Two animal paradigms were utilized; the elevated plus maze (EPM), measuring changes in innate fear of exploration of open spaces; and the social interaction test (SIT), measuring the exploration of a novel, same gender partner. In the EPM, estradiol-treated OVX females both entered and spent more time in the open arms than control OVX females, indicating an anxiolytic-like action of estradiol. In contrast, estradiol treated OVX females interacted less with the partner animal in the SIT compared with controls suggesting anxiogenic-like effects. The possible anxiogenic effect of estradiol in the SIT is supported by two findings: (1) the effect is reversed by the anxiolytic drug alprazolam and (2) estrogen did not affect locomotion and therefore, the reduced social interaction is not due to reduced activity. Acute administration of progesterone (5 mg/kg), which has anxiolytic properties, did not reverse estradiol-induced social interaction deficits, suggesting that lack of progesterone did not account for estradiol's anxiogenic effects. These results, while seemingly contradictory when interpreted within a unified concept of anxiety, may well reflect the ethological roles of reproductive hormones and their effects on different types of exploratory anxiety.     

Bisphenol-A exposure during adolescence leads to enduring alterations in cognition and dendritic spine density in adult male and female rats

We have previously demonstrated that adolescent exposure of rats to bisphenol-A (BPA), an environmental endocrine disrupter, increases anxiety, impairs spatial memory, and decreases dendritic spine density in the CA1 region of the hippocampus (CA1) and medial prefrontal cortex (mPFC) when measured in adolescents in both sexes. The present study examined whether the behavioral and morphological alterations following BPA exposure during adolescent development are maintained into adulthood. Male and female, adolescent rats received BPA, 40 μg/kg/bodyweight, or control treatments for one week. In adulthood, subjects were tested for anxiety and locomotor activity, spatial memory, non-spatial visual memory, and sucrose preference. Additionally, stress-induced serum corticosterone levels and dendritic spine density in the mPFC and CA1 were measured. BPA-treated males, but not females, had decreased arm visits on the elevated plus maze, but there was no effect on anxiety. Non-spatial memory, object recognition, was also decreased in BPA treated males, but not in females. BPA exposure did not alter spatial memory, object placement, but decreased exploration during the tasks in both sexes. No significant group differences in sucrose preference or serum corticosterone levels in response to a stress challenge were found. However, BPA exposure, regardless of sex, significantly decreased spine density of both apical and basal dendrites on pyramidal cells in CA1 but had no effect in the mPFC. Current data are discussed in relation to BPA dependent changes, which were present during adolescence and did, or did not, endure into adulthood. Overall, adolescent BPA exposure, below the current reference safe daily limit set by the U.S.E.P.A., leads to alterations in some behaviors and neuronal morphology that endure into adulthood.     

Effects of ovariectomy and estrogen treatment on learning and hippocampal neurotransmitters in mice

This study examined the effects of long-term estrogen treatment (sc 17 beta-estradiol minipellets) on learning in C57BL/6J female and male mice using a position discrimination task in the T-maze and a win-stay task (1/8 arms baited) in the radial arm maze (RAM). In addition, hippocampal monoamines and ChAT activity were measured at the end of the study and correlated to task performance. Female sham-operated (gonadally intact) and ovariectomized (OVX) mice were treated with estrogen either for 7 or 40 days before the behavioral tests and intact male mice for 7 days before the behavioral tests. In sham-operated mice the 40-day estrogen treatment improved RAM performance and in OVX mice both the 7- and 40-day estrogen treatments improved the performance in both maze tasks. The estrogen treatment also improved RAM performance in males. The hippocampal ChAT, NA, 5-HIAA, and DOPAC levels were decreased in OVX mice. Furthermore, the effects of estrogen treatment on the levels of hippocampal 5-HT and its metabolite 5-HIAA were different in sham-operated than in OVX mice. We could find no correlation between cognitive measures and neurochemical variables. This study gives new information about the effects of estrogen on learning and hippocampal neurotransmitters in mice.     

Gonadotropin induction of ovulation and corpus luteum formation in young estrogen receptor-alpha knockout mice

Estrogen receptor-alpha (ERalpha) knockout (ERalphaKO) female mice are infertile. Initially, they exhibit normal follicular development, but by 4-5 wk of age, they begin to develop hemorrhagic ovarian cysts. Follicles in adult ERalphaKO female mice progress to the graafian stage, but there are no corpora lutea (CL). To test whether ERalpha is required for ovarian folliculogenesis, ovulation, and CL formation, eCG and hCG were used to ovulate 3- to 5-wk-old ERalphaKO and wild-type (WT) sibling mice. Gonadotropin administration resulted in ovulation in both ERalphaKO and WT mice. Gonadotropin-treated ERalphaKO females that ovulated produced 7.09 +/- 0.77 oocytes per mouse, whereas gonadotropin-treated WT female mice had 16.17 +/- 0.84 oocytes. Surprisingly, ruptured ERalphaKO ovarian follicles developed into CL that had normal morphology. Gonadotropin-treated ERalphaKO mice had 3-fold higher concentrations of serum progesterone than did control ERalphaKO mice that had been administered saline rather than gonadotropins. Thus, the CL in gonadotropin-treated ERalphaKO mice appeared to be steroidogenically functional. On the basis of these findings, ovarian folliculogenesis, ovulation, and CL formation can occur in the absence of ERalpha, although to a lesser extent than in WT mice.     

Influence of the estrous cycle on the behavior of rats in the elevated T-maze

The elevated T-maze is an animal anxiety model which can discriminate between anxiety-like and fear-like behaviors. The estrous cycle is an important variable of the response in animal anxiety tests and is known to affect other models. The aim of the present study was to investigate the influence of the estrous cycle on behavior displayed in the elevated T-maze test. Seventeen male and 60 female rats were submitted to one session in this test, with the females being screened for the estrous cycle and divided into groups according to the various phases. The elevated T-maze had three arms of equal dimensions ( 50 cm x 10 cm), one enclosed by 40-cm high walls and perpendicular to the others, the apparatus being elevated 50 cm above the floor. Each rat was placed in the end of the enclosed arm and the latency for it to leave this arm was recorded. These measurements were repeated three times separated by 30-s intervals (passive avoidance). After trial 3, each rat was placed at the distal end of the right open arm and the latency to exit this arm was recorded. Whenever latencies were greater than 300 s the trial was finished. The results demonstrated females in diestrus exhibited anxiety-like behaviors while females in metaestrus behaved in a similar way as the males. There were no differences between groups in fear-like behaviors. The results also indicate the elevated T-maze to be a sensitive test to measure anxiety.     

Sex differences in the long-term effect of preweanling isolation stress on memory retention

Social experiences during development can powerfully modulate later neuroendocrine and behavioral system. In the present study, male and female rat pups experienced daily bouts of social isolation for 6 h per day or control conditions during the third postnatal week. Performance on a 12-arm radial maze with 8 arms consistently baited with food reward was examined in adulthood. During the social isolation, both male and female pups exhibited a significant increase in plasma corticosterone levels. When tested on the radial arm maze as adults, the performance of female rats that had experienced social isolation during development was not affected; however, male rats in the isolation condition initially exhibited impairments in working memory but not reference memory. Despite achieving comparable asymptotic levels of performance on the maze, male rats that experienced social isolation during the third week demonstrated disruption in working memory retention when radial arm maze trials were interrupted after the fourth arm choice. Thus, while male rats that experience social isolation during the third week of life eventually perform comparably to controls on the standard radial arm maze task, their ability to retain information over a delay remains impaired. These findings highlight an important sex difference in the long-term effects of stress during this period of late preweanling development.     

Abnormal vibrissa‐related behavior and loss of barrel field inhibitory neurons in 5xFAD transgenics

A recent study reported lower anxiety in the 5xFAD transgenic mouse model of Alzheimer's disease, as measured by reduced time on the open arms of an elevated plus maze. This is important because all behaviors in experimental animals must be interpreted in light of basal anxiety and response to novel environments. We conducted a comprehensive anxiety battery in the 5xFAD transgenics and replicated the plus‐maze phenotype. However, we found that it did not reflect reduced anxiety, but rather abnormal avoidance of the closed arms on the part of transgenics and within‐session habituation to the closed arms on the part of wild‐type controls. We noticed that the 5xFAD transgenics did not engage in the whisker‐barbering behavior typical of mice of this background strain. This is suggestive of abnormal social behavior, and we suspected it might be related to their avoidance of the closed arms on the plus maze. Indeed, transgenic mice exhibited excessive home‐cage social behavior and impaired social recognition, and did not permit barbering by wild‐type mice when pair‐housed. When their whiskers were snipped the 5xFAD transgenics no longer avoided the closed arms on the plus maze. Examination of parvalbumin (PV) staining showed a 28.9% reduction in PV+ inhibitory interneurons in the barrel fields of 5xFAD mice, and loss of PV+ fibers in layers IV and V. This loss of vibrissal inhibition suggests a putatively aversive overstimulation that may be responsible for the transgenics' avoidance of the closed arms in the plus maze .     

The circadian Clock mutation increases exploratory activity and escape-seeking behavior

Disturbances of circadian rhythms are associated with many types of mood disorders; however, it is unknown whether a dysfunctional circadian pacemaker can be the primary cause of altered emotional behavior. To test this hypothesis, male and female mice carrying a mutation of the circadian gene, Clock, were compared to wild-type mice in an array of behavioral tests used to measure exploratory activity, anxiety, and behavioral despair. Female Clock mutant mice exhibited significantly greater activity and rearing in an open field and a greater number of total arm entries in the elevated plus maze. In addition, female Clock mutant mice spent significantly more time swimming in the forced swim test than wild-type mice on both days of a 2-day test. Male Clock mutant mice also exhibited increased exploration of the open field and increased swimming in the forced swim test; however, behavioral changes were less robust in Clock mutant males compared to Clock mutant females. These changes in behavior were not dependent on the expression of a lengthened free-running period but were more or less striking depending on the testing conditions. These data indicate that the Clock mutation leads to increased exploratory behavior and increased escape-seeking behavior, and, conversely, does not result in increased anxiety or depressive-like behavior. These results suggest that the Clock gene is involved in regulating behavioral arousal, and that Clock may interact with sex hormones to produce these behavioral changes.     

New knockout model confirms a role for androgen receptors in regulating anxiety-like behaviors and HPA response in mice

Men are less likely than women to suffer from anxiety disorders. Because gonadal hormones play a crucial role in many behavioral sex differences, they may underlie sex differences in human anxiety. In rodents, testosterone (T) exerts anxiolytic effects via the androgen receptor (AR): we found that male mice with a naturally-occurring mutation rendering the AR dysfunctional, referred to as spontaneous testicular feminization mutation (sTfm), showed more anxiety-like behaviors than wildtype (WT) males. Here, we used Cre–lox recombination technology to create another dysfunctional allele for AR. These induced Tfm (iTfm) animals also displayed more anxiety-like behaviors than WTs. We further found that AR-modulation of these behaviors interacts with circadian phase. When tested in the resting phase, iTfms appeared more anxious than WTs in the open field, novel object and elevated plus maze tests, but not the light/dark box. However, when tested during the active phase (lights off), iTfms showed more anxiety-related behavior than WTs in all four tests. Finally, we confirmed a role of T acting via AR in regulating HPA axis activity, as WT males with T showed a lower baseline and overall corticosterone response, and a faster return to baseline following mild stress than did WT males without T or iTfms. These findings demonstrate that this recombined AR allele is a valuable model for studying androgenic modulation of anxiety, that the anxiolytic effects of AR in mice are more prominent in the active phase, and that HPA axis modulation by T is AR dependent.     

Severe pulmonary hypertension in aging female apolipoprotein E-deficient mice is rescued by estrogen replacement therapy

Corticotropin-releasing factor overexpressing (CRF-OE) male mice showed an inhibited feeding response to a fast, and lower plasma acyl ghrelin and Fos expression in the arcuate nucleus compared to wild-type (WT) mice. We investigated whether hormones and hypothalamic feeding signals are impaired in CRF-OE mice and the influence of sex. Male and female CRF-OE mice and WT littermates (4–6 months old) fed ad libitum or overnight fasted were assessed for body, adrenal glands and perigonadal fat weights, food intake, plasma hormones, blood glucose, and mRNA hypothalamic signals. Under fed conditions, compared to WT, CRF-OE mice have increased adrenal glands and perigonadal fat weight, plasma corticosterone, leptin and insulin, and hypothalamic leptin receptor and decreased plasma acyl ghrelin. Compared to male, female WT mice have lower body and perigonadal fat and plasma leptin but higher adrenal glands weights. CRF-OE mice lost these sex differences except for the adrenals. Male CRF-OE and WT mice did not differ in hypothalamic expression of neuropeptide Y (NPY) and proopiomelanocortin (POMC), while female CRF-OE compared to female WT and male CRF-OE had higher NPY mRNA levels. After fasting, female WT mice lost more body weight and ate more food than male WT, while CRF-OE mice had reduced body weight loss and inhibited food intake without sex difference. In male WT mice, fasting reduced plasma insulin and leptin and increased acyl ghrelin and corticosterone while female WT showed only a rise in corticosterone. In CRF-OE mice, fasting reduced insulin while leptin, acyl ghrelin and corticosterone were unchanged with no sex difference. Fasting blood glucose was higher in CRF-OE with female > male. In WT mice, fasting increased hypothalamic NPY expression in both sexes and decreased POMC only in males, while in CRF-OE mice, NPY did not change, and POMC decreased in males and increased in females. These data indicate that CRF-OE mice have abnormal basal and fasting circulating hormones and hypothalamic feeding-related signals. CRF-OE also abolishes the sex difference in body weight, abdominal fat, and fasting-induced feeding and changes in plasma levels of leptin and acyl ghrelin.     

Effects of 5-HT1A receptor agonist and antagonist on anxiety in intact and ovariectomized female rats

The purpose of this work was to study the role of 5-HT1A receptors on the level of anxiety in adult intact and ovariectomized (OVX) female rats. The influence of chronic administration of 5-HT1A receptor agonist 8-OH-DPAT (0.05 mg/kg, s.c.) and 5-HT1A receptor antagonist NAN-190 (0.1 mg/kg, i.p.) given for 14 days alone or in combination with 17beta-estradiol (0.5 microg i.m./rat/day) was studied on behavior in the elevated plus maze. In intact females administration of NAN-190 resulted in significant increase in the number of enterings and the time spent on the open arms in every phase of the estrous cycle, however, 8-OH-DPAT failed to modify these parameters. In OVX females 8-OH-DPAT alone or in combination with 17beta-estradiol significantly increased the number of enterings and time spent on the open arms. On the contrary, NAN-190 alone or in combination with 17beta-estradiol in OVX females failed to evoke behavioral changes in the elevated plus maze. Thus, the 5-HT1A receptor antagonist NAN-190 induced anxiolytic effect in intact female rats, while 5-HT1A receptor agonist 8-OH-DPAT produced an anxiolytic profile on OVX rats. Results of this work specify the involvement of 5-HT1A receptors in behavioral mechanisms of anxiety in OVX female rats.     

Differences in anxiety-related behavior between apolipoprotein E-deficient C57BL/6 and wild type C57BL/6 mice

The influence of ApoE gene deletion on the anxiety state has not been previously investigated. The elevated plus maze was used in this study to determine differences in anxiety-related behavior between apoE-deficient and wild type C57BL/6 mice. The apoE-deficient mice demonstrated less anxiety on the elevated plus maze by spending more time in the open arms of the elevated plus maze compared to wild type mice (p<0.001). Additionally, female apoE-deficient mice visited the open arm of the maze more often than their apoE-deficient male counterpart (p<0.05). The anxiety state and/or sex are possible variables to be considered when designing physiological and/or behavioral studies involving mice that are apoE-deficient.     

Evidence of Mate Trailing in the Giant Hairy Desert Scorpion, Hadrurus arizonensis (Scorpionida, Iuridae)

During the mating season, male desert scorpions are often found wandering through dune environments, presumably in search of female conspecifics. For a male desert scorpion, finding a receptive female is a potentially difficult and hazardous task, suggesting that wandering by the male may actually be a form of guided mate searching. In this study we examined whether male giant hairy desert scorpions (Hadrurus arizonensis) were capable of trailing female conspecifics using a Y-maze choice test. In three separate experiments, a significant proportion of male scorpions preferred the arm of the maze that a reproductive female scorpion had walked down. Male scorpions did not prefer maze arms that male conspecifics had walked down, indicating that this response was sex specific. When the substrate was repeatedly exposed to a reproductive female, males took significantly longer to complete the Y-maze test, exhibited an increase in pausing behavior, and displayed precourtship behaviors and a novel lunging behavior resembling sex-specific mate seizing behavior. The results from this study suggest that male H. arizonensis can orient and respond to substrate-borne signals from female conspecifics that are likely chemical in origin.     

Cues used by male and female hooded rats for locating a brightness change

Entries of and time spent in a novel Y-maze arm that had changed from white (during acquisition trials) to black (during retention trials) were investigated in male and female Long-Evans hooded rats after the apparatus had been horizontally rotated through 180 degrees or left undisturbed. Maze rotation reduced responsiveness to this arm in males but not in females. When each arm was associated with a different set of visual cues, males significantly chose the novel arm only in the presence of intra- and extra-maze cues either alone or in combination. Females significantly selected the novel arm only in the absence of either type of cue, and in the presence of intra-maze cues alone. However, when the duration of acquisition trials was increased from 6 to 12min, females also selected the novel arm in the presence of both intra- and extra-maze cues. It was concluded that, while female rats appeared able to use egocentric (or response-related) cues for locating the novel arm, males were more dependent on allocentric (or place-related) cues following shorter acquisition trials. Because of the importance of such cues, it seemed that the task of recognizing which maze arm had changed in brightness defined the test as one of spatial memory.     

Sex-related effects of sleep deprivation on depressive- and anxiety-like behaviors in mice

Anxiety and depressive symptoms are generated after paradoxical sleep deprivation (PSD). However, it is not clear whether PSD produces differential effects between females and males. The aim of this study was to assess the effect of PSD on anxiety- and depressive-like behaviors between sexes. Male and female BALB/c mice were divided in three groups: the control group, the 48-h PSD group and the 96-h PSD group. Immediately after PSD protocols, the forced swimming and open field test were applied. Sucrose consumption test was used to evaluate the middle-term effect of PSD. We found that corticosterone serum levels showed significant differences in the 96-h PSD females as compared to 96-h PSD males. In the open-field test, the 48-h and 96-h PSD females spent more time at the periphery of the field, and showed high locomotion as compared to males. In the elevated plus maze, the 48-h PSD females spent more time in closed arms than males, which is compatible with anxiety-like behavior. The forced swim test indicated that the 96-h PSD males spent more time swimming as compared to the 96-h PSD females. Remarkably, the 96-h PSD males had lower sucrose intake than the 96-h PSD females, which suggest that male mice have proclivity to develop a persistent depressive-like behavior late after PSD. In conclusion, male mice showed a significant trend to depressive-like behaviors late after sleep deprivation. Conversely, female have a strong tendency to display anxiety- and depressive-like behaviors immediately after sleep deprivation.     

Mice with the testicular feminization mutation demonstrate a role for androgen receptors in the regulation of anxiety-related behaviors and the hypothalamic–pituitary–adrenal axis

Testosterone (T) appears to play a role in anxiety and sensorimotor gating in rodents, but whether T acts through the androgen receptor (AR) to influence these behaviors is less clear. We compared adult genetic male mice with the testicular feminization mutation (Tfm), which lack functional ARs, to wild type male littermates (wt males) on an assay of sensorimotor gating (prepulse inhibition of the acoustic startle response; PPI) and several tests thought to reflect anxiety: open field exposure, novel object exposure, elevated plus maze (EPM), and light/dark (LD) box. PPI was similar between groups, but indices of anxiety in the novel object and LD box tests were increased in Tfm males with no significant differences found in the open field or EPM. Since Tfm male mice have decreased circulating T, the same tests were conducted in mice that were gonadectomized (wt males) or sham-operated (Tfm males) as adults and supplemented with T or nothing (B). While T treatment reduced indices of anxiety in the novel object and LD box tests in wt males, it was ineffective in Tfm males. Increased indices of anxiety in Tfm males appear to be related to hyper-activation of the hypothalamic–pituitary–adrenal axis since levels of the stress hormone corticosterone were elevated in Tfm males compared to wt males at baseline and at several time points after exposure to a novel object. These findings demonstrate that ARs influence anxiety and stress responses in mice.     

Partner preference of intact and ovariectomized female gray short-tailed opossums (Monodelphis domestica)

Intact, ovariectomized and ovariectomized estradiol (E)-treated female gray short-tailed opossums were placed in a test situation in which they could choose between an intact and a castrated male. Intact females chose to visit intact males first and visited them more frequently and spent more time with intact than with castrated males. Ovariectomized (OVX) females did not show this preference for visiting intact males over castrates. When compared to OVX females with blank implants, OVX females with E implants spent less time with castrated males. Like intact females, OVX and OVX-E-treated females preferred to stay in close proximity to but not actually in the cage of intact rather than castrated males. To our knowledge, this is the first experimental study of partner preference and its relationship to hormonal condition in a female marsupial.     

Sex differences and sex hormones in anxiety-like behavior of aging rats

Sex differences in the prevalence of affective disorders might be attributable to different sex hormone milieu. The effects of short-term sex hormone deficiency on behavior, especially on anxiety have been studied in numerous animal experiments, mainly on young adult rats and mice. However, sex differences in aged animals and the effects of long-term hypogonadism are understudied. The aim of our study was to analyze sex differences in anxiety-like behavior in aged rats and to prove whether they can be attributed to endogenous sex hormone production in males. A battery of tests was performed to assess anxiety-like behavior in aged female, male and gonadectomized male rats castrated before puberty. In addition, the aged gonadectomized male rats were treated with a single injection of estradiol or testosterone or supplemented with estradiol for two-weeks. Female rats displayed a less anxious behavior than male rats in most of the conducted behavioral tests except the light-dark box. Long-term androgen deficiency decreased the sex difference in anxiety either partially (open field, PhenoTyper cage) or completely (elevated plus maze). Neither single injection of sex hormones, nor two-week supplementation of estradiol in gonadectomized aged male rats significantly affected their anxiety-like behavior in the elevated plus maze. In conclusion, our results confirm sex differences in anxiety in aged rats likely mediated by endogenous testosterone production in males. Whether long-term supplementation with exogenous sex hormones could affect anxiety-like behavior in elderly individuals remains to be elucidated.     

Anxiety and fear behaviors in adult male and female C57BL/6 mice are modulated by maternal separation

This study investigated the effects of maternal separation in C57BL/6 male and female mice during infancy on later adult fear and anxiety behaviors. Additionally, we observed the maternal behavior of the dams to examine aspects of maternal care that may be modulated by daily bouts of separation. In males, mice that experienced maternal separation during the neonatal period displayed significantly higher levels of anxiety and fear behavior, as measured by the open field test and elevated plus maze, compared to control, standard facility reared males. In females, however, maternal separation reduced anxiety and fear behavior in the open field test, but only when the females were in the diestrous phase of their estrous cycle. The 30-min daily observation of the dams revealed that the separation did not significantly alter the frequency of the maternal care provided by the dam at the time point measured. These results indicate that the emotionality of adult male and female mice can be modulated by maternal separation. However, this effect is dependent on the sex of the offspring and the phase of the estrous cycle of the female.