Neonatal handling increases fear and aggression in lactating rats

Neonatal handling reduces fear in male and cycling female rats, but increases maternal aggressive behavior against intruders to the nest area. Present study aimed to analyze the effects of neonatal handling on the maternal aggressive behavior and the activity in the open field with a predator of lactating rats on the 8th and the 18th postpartum days (periods of high and low aggressiveness). As pups, animals were divided into two groups: nonhandled (no neonatal manipulation) and handled (handling for 1 min during the first 10 days after delivery). As adults, females of both groups were impregnated and tested against a male intruder for aggressive behavior and in the open field with a cat inside a wire-meshed cage. Results showed that on the 8th day frequency of aggressive behaviors of handled females was higher than that of the nonhandled ones, but on the 18th day, no significant difference was detected. Surprisingly, in the open field test, handled females showed decreased locomotion and increased freezing on the 8th day compared to the nonhandled ones. The opposite relationship between increased aggressiveness with reduced fear is observed in the nonhandled control females in early and late lactation periods. However, neonatal handling abolishes this relationship. Apparently, the increased aggressiveness in neonatal handled lactating females does not depend on a decrease in fear. Our findings support the hypothesis that long lasting effects of early life stimulation is a dynamic function depending on the behavioral system and the period of life analyzed. Moreover, they caution the relationship between aggressive behavior and fear.     

Isolation-induced locomotor hyperactivity and hypoalgesia in rats are prevented by handling and reversed by resocialization

Differences in locomotor activity in the open field were found between individually and group-housed rats (isol greater than soc). Daily handling, initiated at postnatal day 1, was without effect in group-housed rats but prevented the isolation-induced hyperactivity. For tail-flick latency, strikingly similar differences (isol greater than soc; prevention by handling) have been observed. The isolation-induced aberrations in both locomotor reactivity in a novel environment and in pain sensitivity could be reversed by subsequent resocialization. This indicates that the altered sensitivities to external stimuli are caused by the environmental manipulation.     

Brain stimulation enables the solution of an inherently difficult problem

Lactating female rats show a maternal anxiolysis signal, which is part of the behavioral pattern that develops post-partum and seems to be related to hormonal changes during lactation. Assuming that glucocorticoids modulate prolactin and oxytocin secretion, we evaluated the effect of dexamethasone on behavior responses of fear and anxiety in lactating rats. For this study, the non-lactating and lactating rats were submitted to an elevated T-maze and open field tests. In the elevated T-maze, the lactating rats showed a decrease in inhibitory avoidance and an increase in the escape time when compared with the non-lactating group. The lactating rats that had been treated with dexamethasone showed increased initial avoidance latency when compared with lactating rats treated with vehicle. The same result was found in the subsequent repetitions (avoidance 1 and 2). In addition, there was a reduction in one-way escape time for the lactating rats that were treated with dexamethasone. The lactating rats treated with vehicle had increase of number central entries, and consequently, the anti-thigmotactic effect increased relative to non-lactating rats. Thus, lactating rats showed a reduced emotional responsiveness as evaluated by elevated T-maze and open field tests, which characterizes maternal anxiolysis. In addition, it could be concluded that the dexamethasone impairs maternal anxiolysis in lactating female rats.     

Motor activity (exploration) and formation of home bases in mice (C57BL/6) influenced by visual and tactile cues: modification of movement distribution, distance, location, and speed

The motor activity of mice in tests of "exploration" is organized. Mice establish home bases, operationally defined as places where they spend long periods of time, near physical objects and nesting material from which they make excursions. This organization raises the question of the extent to which mouse motoric activity is modulated by innate predispositions versus environmental influences. Here the influence of contextual cues (visual and tactile) on the motor activity of C57BL/6 mice was examined: (1) on an open field that had no walls, a partial wall, or a complete wall, (2) in the presence of distinct visual cues, room cues, or in the absence of visual cues (infrared light), and (3) in the presence of configurations of visual and tactile cues. Mice were generally less active in the presence of salient cues and formed home bases near those cues. In addition, movement speed, path distribution, and the number and length of stops were modulated by contextual cues. With repeated tests, mice favored tactile cues over visual cues as their home base locations. Although responses to cues were robust over test days, conditioning to context was generally weak. That the exploratory behavior of mice is affected by experience and context provides insights into performance variability and may prove useful in investigating the genetic and neural influences on mouse behavior.     

Effects of impaired testosterone metabolism during prenatal ontogenesis on the level of anxiety and behavior of rats in a novel environment

The effects of administration of the aromatase inhibitor 1,4,6-androstatrien-3.17-dione (ATD) to female rats during the last third of pregnancy on the formation of behavior of offspring of both genders in a novel environment were studied. Animal behavior was assessed in the open field and elevated cross maze tests. Inhibition of testosterone aromatization during the prenatal period of development resulted in increases in anxiety and emotionality in experimental rats at age one month; increases in these measures in adult animals were seen in both males and females exposed to prenatal ATD. Intergender differences between control males and experimental females, in terms of behavioral measures in the novel environment such as motor activity, the duration of the freezing and grooming reactions, as well as well the level of anxiety, disappeared. It is concluded that impairment of testosterone metabolism during the prenatal period of development affects the formation of the behavior of rats in a novel environment as determined by genetic gender. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 56, No. 3, pp. 338–344, May–June, 2006.     

Characteristics of behavior and stress reactivity of the hypophyseal-adrenocortical system in rats with prenatal inhibition of testosterone metabolism

The effects of administration of the aromatase blocker 1,4,6-androstatrien-3,17-dione (ATD) to female rats in the last third of pregnancy on the stress reactivity of the hypophyseal-adrenocortical system (HACS), behavior in a novel environment (an open field), and anxiety in an elevated cross maze in their adult offspring of both genders were studied. Inhibition of testosterone aromatization in the brain during the prenatal period of development was found to lead to a decrease in the basal activity of the HACS in males and longer-lasting hormonal stress responses in animals of both genders. However, the intergender differences in the nature of the stress reactivity of the system in the experimental animals persisted. Prenatal administration of ATD also induced increases in the levels of anxiety and emotionality and the duration of grooming reactions in males and females and eliminated intergender differences between control males and experimental females in terms of measures of behavior in a new environment such as movement activity, duration of the freezing reaction, and grooming. These data led to the conclusion that impaired testosterone metabolism in the brain during the prenatal period of development induced by administration of the aromatase blocker leads to changes in the nature of the stress response of the HACS in adult male and female rats and impairs the formation of sexual dimorphism in anxiety levels and the extent of behavioral reactions to environmental novelty in females. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 91, No. 9, pp. 1071–1079, September, 2005.     

Maternal treadmill exercise during pregnancy decreases anxiety and increases prefrontal cortex VEGF and BDNF levels of rat pups in early and late periods of life

In a previous study we demonstrated that, regular aerobic exercise during pregnancy decreased maternal deprivation induced anxiety. The purpose of this study is to investigate whether the positive effects of maternal exercise on the male and female offspring's early and late period of life. Half of the test subjects in each group were evaluated when they were 26 days old, and the other half were evaluated when they were 4 months old. The anxiety levels of maternally exercised groups were less than the control groups in both sexes and in both prepubertal and adult periods. The locomotor activity more increased in females. The prefrontal VEGF and BDNF levels were greater for both age groups and sexes in the maternally exercised group compared to control group. Moreover, there was a strong positive correlations between prefrontal cortex BDNF levels and results of open field tests; and VEGF levels and results of elevated plus maze tests. There was no difference in serum corticosterone levels between groups. These results indicate that maternal exercise during pregnancy may protect the pups from anxiety in early and late periods of life, and affects the prefrontal cortex positively.     

Effects of early environmental enrichment upon open-field behavior and timidity in the domestic chick

Early environmental enrichment was evaluated by its effect on the behavior of 7-day-old male and female domestic chicks in an open field or novel environment and in a hole-in-the-wall test of timidity. The chicks were housed in same-sex groups of 10. The bare environments contained wood litter, food, and water, whereas the enriched boxes also contained various objects. In the open field, immobility was lower while feeding, walking, jumping and vocalization were higher in the enriched birds than in those reared in the bare environment. Enrichment also decreased emergence latencies in the hole-in-the-wall box. The increased stimulation provided by environmental enrichment may decrease fearfulness in subsequent fear-inducing situations and may enhance the ability of animals to adapt to novelty.     

Social play with an unfamiliar group in weanling rats (Rattus norvegicus)

Early signs of aggressive behavior toward an intruder were examined in Sprague-Dawley rats. The interactions between groups of four 24-day-old pups (2 males, 2 females) and an unfamiliar male pup from another litter were observed. Some patterns of social play were asymmetric. Compared to the playmate from the group, the unfamiliar pup was most likely to be underneath the other rats, either during play fighting or by crawling under a playmate. The single pup was most frequently involved in the following behaviors: on top (One animal climbs on top of another animal placing its forepaws on the second animal.), grooming, or crawling under a playmate. The effects of relative birth weight, ambient temperature during the lactation period, relative body weight, and relative body temperature during the observation period were studied. Results show that pups born and raised in a warm environment interacted socially more than pups raised in a colder environment. Pups lighter than the mean body weight of playmates tended to use submissive behaviors more than relatively heavier pups. Relatively heavy pups tended to use play behaviors that might be considered more aggressive during the interaction. The results suggest that under appropriate conditions, early evidence for dominance, i.e., asymmetry can be revealed. © 1997 John Wiley & Sons, Inc. Dev Psychobiol 30: 165–176, 1997     

Effects of nutrition and environment on brain biochemistry and behavior

A factorial design was used to explore the influence of malnutrition and environmental enrichment on brain development and adult behavior. Malnutrition in suckling rats was produced by restricting the intake of their dams to 40% of normal food consumption. Environment was enriched using combined preweaning handling and a postweaning complex environment treatment. Malnutrition produced lasting effects upon brain biochemical composition and behavior. The environmental manipulation had no ameliorative effect on the brain parameters measured but it had pronounced effects on behavior, decreasing latency to move in the open field and increasing some measures of activity while it enhanced passive-avoidance performance. There was little evidence for any interaction between the nutritional and environmental variables, but all trends were in the direction of the environmental treatment having more effect on the well-nourished rats.     

Effects of parental environment on the prevalence of convulsive seizures in Onychomys torridus

Male and female southern grasshopper mice (Onychomys torridus) were reared in 1 of 3 different parental environments: (a) with the natural male and female parents; (b) with the female parent only; or (c) with foster parents of a closely related species, Peromyscus leucopus. All mice were weaned at 25 days of age, then observed individually in an open field arena at 10-day intervals from 30 to 100 days of age. Twenty-seven of 59 subjects (45.8%) that were reared by the natural parents exhibited convulsive seizures during at least 1 of the 8 tests in the open field arena. The prevalence of convulsive seizures increased significantly in subjects that received altered parental care: 27 of 41 subjects (65.9%) reared by the female parent only or by Peromyscus foster parents seized during at least 1 of the 8 tests in the open field. Subjects from the 3 treatment groups did not differ in the mean number of seizures observed during the 8 open field tests. These results demonstrate a significant influence of the preweaning parental environment on the prevalence of convulsive seizures in Onychomys torridus.     

Effect of dietary protein and environmental factors on lactation performance in rats.

The effects of dietary protein and environmental conditions on lactation performance in rats were evaluated. Female rats were fed from conception until day 9 of lactation diets containing 21% wheat protein (21W), 21% casein + methionine (21CM) or 11% casein + methionine (11CM). At parturition, dams were kept in their normal environment (20 degrees C) or were exposed to crowded conditions or an elevated ambient temperature (30 degrees C). Feeding poor-quality protein (21W) or a lower amount of high-quality protein (11CM) reduced day 8 pup weights and average daily gains (ADG). Pup ADG's nursed by crowded dams fed either 11CM or 21CM were greater than those of pups nursed by noncrowded dams. Pup ADG's were reduced by heat exposure in dams fed 21CM but not in pups raised by dams fed diets reduced either in protein quality (21W) or protein quantity (11CM). Thus lactation performance was not further reduced by heat exposure in dams fed poor-quality wheat protein in spite of reduced food consumption and increasing lactation weight loss in these dams. The study indicates that lactating rats have considerable ability to raise their litters under potentially adverse conditions.     

Variability in "spontaneous" maternal behavior is associated with anxiety-like behavior and affiliation in naïve juvenile and adult female prairie voles (Microtus ochrogaster)

Juvenile female prairie voles (Microtus ochrogaster) are spontaneously maternal, while virgin adult females show significant variability in their response to first pup exposure, ranging from infanticidal to full maternal behavior. In the present study, we investigated whether differences in anxiety-like behavior and affiliation are associated with juvenile-adult and adult individual differences in the response to pups. Forty juvenile (19-20 days) and 42 adult (60-90 days) female prairie voles were exposed to pups for the first time and tested for maternal behavior, anxiety-like behavior (elevated plus maze, open field), and affiliation toward age-matched, same sex conspecifics. Juveniles displayed less anxiety-like behavior, were more affiliative to unfamiliar conspecifics, and interacted with pups more positively than adults. Adults that displayed maternal behavior spent less time immobile, made more crosses through the center of the open field arena, and were more affiliative than adults that attacked the pups. This suggests that lower locomotion or exploration in a novel environment and poor affiliative behavior are negatively associated with maternal responsiveness in female prairie voles.     

Comparative analysis of anxiety-like behaviors and sensorimotor functions in two rat mutants, ci2 and ci3, with lateralized rotational behavior

There is increasing evidence that developmental anomalies of cerebral asymmetry are involved in the etiology of psychiatric disorders, including schizophrenia, depression and anxiety. Thus, rodents with abnormal cerebral lateralization are interesting tools to study the association between such anomalies and behavioral dysfunction. The most studied indicator of cerebral asymmetry in the rat is that of circling or rotational behavior. We have recently described two rat mutants, ci2 and ci3, in which lateralized rotational behavior occurs either spontaneously or in response to external stimuli, such as new environment or handling. While cochlear and vestibular defects are found in 52 rats, ci3 rats do not exhibit any inner ear abnormalities. The abnormal motor response to external stimuli raised the possibility that the circling rat mutants may be more likely to express anxiety-related behavior in tests of emotionality. In the present study, we characterized anxiety-related behaviors of ci2 and ci3 rats in the open field, elevated plus-maze and light/dark exploration test. Furthermore, sensorimotor functions of these rats were evaluated by the rotarod, accelerod and wire hang tests. Heterozygous (ci2/+) littermates or rats of the respective background strains (LEW, BH.7A) were used as controls. In contrast to our expectation, both mutants demonstrated less anxiety-related behavior than controls in tests of emotionality. Ci3 rats exhibited normal sensorimotor functions, whereas marked impairment was observed in ci2 rats, which is most likely a consequence of the vestibular dysfunction in these animals. The acoustic startle response (ASR) and prepulse inhibition of ASR did not differ between ci3 rats and controls. The reduced emotionality of the mutant rats indicated by the present experiments may not be specifically linked to anxiety per se, but is maybe more reflective of impulsivity or the inability to normally perceive or process potentially threatening situations. Based on previous findings of dysfunctions of the central dopamine system in ci2 and ci3 mutant rats, we assume that alterations in dopaminergic activity are involved in the maladaptive behavior observed in the present study.     

Effect of mothering on the spatial exploratory behavior of quail chicks

Previous maternal deprivation experiments demonstrated that absence of maternal care impacts the behavioral development of young animals. Here we assessed the influence of the presence of a mothering hen on the spatial exploration of Japanese quail chicks, after the mothering period. Brooded and nonbrooded chicks were placed in a novel environment containing feeding troughs. The distribution of chicks and their inter‐individual distances were measured during repeated tests. Brooded chicks exhibited a higher ability to disperse, thereby progressively exploiting larger surfaces and gaining access to food more easily. The fact that exploration by nonbrooded chicks was delayed suggests a deficit in their exploratory motivation and/or spatial skills. We hypothesize that brooded chicks experienced the constraint to follow the mothering hen, and to adapt to frequent reconfigurations of their environment. The lack of this variability in the environment of nonbrooded chicks could have reduced adaptability of their spatial behavior. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 256–264, 2013     

Comparison of the effects of the mother and an unfamiliar adult female on cortisol and behavioral responses of pre- and postweaning guinea pigs

In the guinea pig, the presence of the mother, but not littermates, has been found to inhibit hypothalamic-pituitary-adrenal (HPA) responses during brief (30-60 min) exposure to novel surroundings both prior to and several weeks following the completion of weaning. In the present study, we found that an unfamiliar adult female inhibited plasma cortisol and vocalization responses of pre- and postweaning guinea pigs during a 60-min exposure to a novel environment. However, the presence of the mother still had a greater effect on the cortisol levels of the young, at least during the preweaning period. The moderating influence of the unfamiliar adult female on vocalizations and cortisol levels occurred despite behavioral interactions, such as heightened aggression and sexual behavior, not seen during tests with the mother. It is suggested that the unfamiliar adult female's effectiveness in reducing HPA activity during exposure to novelty may facilitate the change in patterns of social interaction occurring in recently weaned animals.     

Sex differences in anxiety-like behavior and locomotor activity following prenatal and postnatal methamphetamine exposure in adult rats

The aim of the present study was to investigate the impact of prenatal and postnatal methamphetamine (MA) exposure on behavior and anxiety in adult male and female rats. Mothers were daily exposed to injection of MA (5 mg/kg) or saline (S): prior to impregnation and throughout gestation and lactation periods. On postnatal day 1, pups were cross-fostered so that each mother raised 6 saline-exposed pups and 6 MA-exposed pups. Based on the prenatal and postnatal exposure 4 experimental groups (S/S, S/MA, MA/S, MA/MA) were tested in the Open field (OF) and in the Elevated plus maze (EPM) in adulthood. Locomotion, exploration, immobility and comforting behavior were evaluated in the OF, while anxiety was assessed in the EPM. While prenatal MA exposure did not affect behavior and anxiety in adulthood, postnatal MA exposure (i.e. MA administration to lactating mothers) induced long-term changes. Specifically, adult female rats in diestrus and adult males postnatally exposed to MA via breast milk (S/MA and MA/MA) had decreased locomotion and exploratory behavior in the OF and showed increased anxiety-like behavior in the EPM when compared to female rats in diestrus or males postnatally exposed to saline (S/S and MA/S). In adult females in proestrus, postnatal exposure to MA affected only exploratory behavior in the OF when compared to rats in proestrus postnatally exposed to saline. Thus, the present study shows that postnatal exposure to MA via breast milk impairs behavior in unfamiliar environment and anxiety-like behavior of adult male and female rats more than prenatal MA exposure.     

Testosterone, social and sexual behavior of perinatally and lifelong calorie restricted offspring

Calorie restriction (CR) during sensitive perinatal periods has consistently been demonstrated to alter the development of a variety of physiological systems, which consequently affect behavior. This study compared the social behavior and sexual behavior of the adult male offspring of mothers administered a 25% CR at one of four times in the perinatal period: a brief period preconception, during gestation, during lactation, or a lifelong restriction (beginning at conception and continuing throughout life). Levels of serum testosterone were also determined in these animals. Social interaction increased in the gestation and lifelong CR groups. The lifelong group also exhibited more dominant type behaviors. CR during preconception and lactation resulted in offspring that displayed an enhanced and more efficient copulatory pattern compared to all other conditions. This was demonstrated by a reduced frequency of intromissions, shorter latency to ejaculation, and a greater frequency of ejaculations by the preconception and lactation group compared to some, if not all of the other CR groups and controls. Serum testosterone was significantly higher in the preconception group compared to controls. These findings indicate that CR during specific periods of development can differentially alter the social behavioral phenotype and hormone levels in adulthood.     

Activation of aggression in female rats by normal males and by castrated males with testosterone implants

Female hooded rats were continuously housed with an intact male, a castrated male with subcutaneous testosterone implants, or two other females. At weekly intervals over a 10-week period, the cagemate(s) and pups were removed and aggression by the female toward an unfamiliar female intruder was observed over a 15-min period. On the 11th week each female was subjected to this intruder test in an unfamiliar cage. On the 12th week, a final test was conducted in each female's living cage with a male rather than a female as the intruder. The aggressive behaviors recorded were attacks, bites, on-top, and piloerection. Females housed with normal males displayed a significant increase in aggression prior to parturition. Their aggressiveness persisted through the 10th test with peaks at parturition and the start of lactation. Females housed with castrated males also displayed significant increases in aggression but without the peaks associated with parturition and lactation. Their aggressiveness also persisted throughout the test period. Females housed with other females showed a small increase in aggression over weeks. All groups showed virtually no aggression in the unfamiliar cage. All females displayed some aggression toward a male intruder but the level of aggression was highest in maternal females. The results demonstrate that aggression qualitatively similar to that displayed following parturition and during lactation can be elicited in nulliparous females.     

Social stress in mice: gender differences and effects of estrous cycle and social dominance.

A large discrepancy in the possibility of inducing social stress in the two genders exists. Since generalizations of findings from one sex to the other appear not to be valid, reliable models of social stress in females are needed. We examined the effects of social context in the housing environment, as a possible source of stress, on exploration and anxiety in male and female mice, taking into account the estrous phase for females and the social status for males as additional variables. Mice housed individually or with siblings were tested in a free-exploratory paradigm of anxiety (where test animals have a choice to stay in their home cage or to explore an open field, OF). Individually housed females did not leave their home cage for long periods, explored less the unfamiliar area and displayed higher risk assessment, a behavioral profile suggestive of lower propensity for exploration and higher level of anxiety compared with group-housed females. Individually housed males tended to show an opposite profile. Proestrus mice were less sensitive to the decrease of exploratory propensity induced by individually housing compared to estrus and diestrus mice. Social dominants and social subordinates in sibling groups did not differ in their exploratory responses to the OF. Different housing procedures, as means to provide different social environment, may differentially induce mild social stress in male and female mice.