Programming life histories: An experimental design and initial results

The life experiences of rats were experimentally programmed through the systematic manipulation of several social and stress variables. These were (1) infantile handling vs. no handling of the mothers of the subjects, (2) infantile handling vs. no handling of the subjects, (3)rearing of the subjects in either a maternity cage or a free environment between birth and weaning, (4) rearing of the subjects in either a laboratory cage or a free environment between weaning and 42 days of age, and (5) presence or absence of a stress experience (shuttlebox avoidance learning at 70 days of age, or food and water deprivation at 100 days) in adulthood. Test measures included open-field performance and shuttlebox learning at 70 and 190 days of age. Open-field activity was increased by handling pups in infancy and by rearing pups in a free environment between birth and weaning, whereas it was decreased by food and water deprivation at 100 days. Postweaning free-environment experience improved avoidance learning performance. A number of interactions were significant, most of which involved the three preweaning variables of Mother Handling, Offspring Handling, and Preweaning Housing.     

Experimental programming of life histories: Toward an experimental science of individual differences

Four experimental variables were combined in a 2 × 2 × 2 × 2 factorial design. These were (1) infantile handling vs. no handling of the mothers of the subjects, (2) infantile handling vs. no handling of the subjects, (3)rearing of the subjects in either a maternity cage or a free environment between birth and weaning, and (4) rearing of the subjects in either a laboratory cage or a free environment between weaning and 42 days of age (N = 6 Purdue-Wistar rats per group). Starting at 220 days of age, the groups were given a battery of tests which measured emotional reactivity, exploratory behavior, and consumption-elimination. Analysis of the criterion data revealed the following: (1) handling pups in infancy reduced emotional reactivity and this reduction was found to be invariant with respect to different combinations of life history experiences; (2) exploratory behavior was markedly influenced by the animal's pattern of life experiences; (3) when mothers were handled during their infancy, their offspring explored significantly less than offspring of nonhandled mothers.     

Effects of male odor during infancy on the maturation, behavior, and reproduction of female mice

Infant female mice who were exposed to the odor of adult male mice of the same strain in the presence or absence of the mother were compared with mice who were not exposed with respect to maturation, open-field behavior, and reproductive success. Exposure lasted 4 hr daily during days 4–18 post-partum. No significant differences were found between the groups in their rates of growth or the age of ear, eye, and vaginal opening. However, the exposed groups displayed first estrus significantly earlier than non-exposed groups: the group exposed in the presence of the mothers showing the earliest first estrus of all 4 groups.     

Maternal and infantile influences upon exploratory behavior and emotional reactivity in the albino rat

A 2 × 2 × 2 factorial experiment was conducted to investigate the combined effects of maternal infantile handling, maternal pregnancy (offspring pre-natal) stress, and offspring infantile handling on adult open-field behavior and weight of albino rats. The primary results are as follows: (1) both offspring infantile handling and maternal pregnancy stress tend to increase adult exploratory behavior; (2) adult weight was lower for subjects whose mother had undergone stress during pregnancy than for offspring of non-stress females; (3) several 2-way interactions were found to significantly influence open-field exploration; (4) when offspring infantile handling was combined with maternal pregnancy stress, emotional reactivity (i.e., defecation) was found to increase significantly over that following either type of stimulation alone.     

Infantile stimulation and ultrasonic signaling: a possible mediator of early handling phenomena

Peromyscus maniculatus bairdi were either handled or not handled daily during the first 10 days of life. Handling consisted of removing the infant mice from the litter, placing them in small individual compartments where they remained for 3 min, and then replacing them in the nest. Immediately following the handling, simultaneous video and audio recordings were made of nest behavior for two 30-sec recording sessions. The nonhandled controls were treated comparably except that pups were never removed from the nest. Handled litters differed from nonhandled in terms of the average number of signals per recording session (132.5 vs. 16.5), the average signal duration (0.108 sec vs. 0.045 sec), and the average peak frequency of signals (22.216 kHz vs. 11.990 kHz). During those recording sessions in which no vocalizations were detected no physical interaction appeared between the mother and the infants. During all sessions in which vocalizations were emitted the mother was retrieving and grooming the infants. The data suggest a possible interpretation of the effects of early handling in terms of modified mothering, medidiated by modified vocalizations of infant mice as a function of the handling.     

The confounding effects of genetic variables in early experience research: Can we ignore them?

The high probability that the genetic makeup of different subject populations within a species will interact with treatment effects in early experience studies suggests that major revisions in both research methodology and interpretations of results are necessary in this area. Generalizations based on data from a single subpopulation of a species can be misleading, especially if they are based on a limited number of behavioral measures.     

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.     

Effects of maternal care on the development, emotionality, and reproductive functions in male and female rats

Variations in maternal behavior induce long-lasting effects on behavioral and neuroendocrine responses to stress. The aim of this study was to analyze developmental parameters, reproductive function, and anxiety-related behaviors of male and female rats raised by mothers that naturally display high and low levels of maternal licking behavior. Results showed that an increase in licking behavior received by the pups accelerated their eye opening and reduced fear behavior assessed in the open field test. Additionally, female offspring of high licking (HL) mothers showed decreased ovulation and lordosis intensity. In contrast, males from HL and low licking (LL) mothers did not differ in their reproductive function, suggesting a gender difference in maternal effects. Present results showed that individual differences in maternal behavior appear not only to be predictive of later emotionality and stress-responsivity in the offspring, but can also modulate the reproductive function of females. Maternal genetic factors, differences in the prenatal intrauterine milieu, or a combination of these cannot be excluded to explain the effects observed.     

Development of open-field behavior in mice: Effects of age and experience

Offspring from each of two inbred strains of mice (BALB/cJ and C57BL/6J) and their reciprocal crosses were tested in an open-field apparatus at 10 ages, from 15 to 120 days. Cross-sectional and longitudinal analyses were performed to assess separately the effects of age and prior test experience on open-field activity and defecation. Increased activity was associated with increased age in both strains and their F₁ reciprocal hybrids; however, the magnitude of this effect was a function of the genotype. Defecation also increased initially in all groups as a function of age; but, at later ages, different groups exhibited rather dissimilar defecation patterns. Prior experience was found to decrease activity in the open field in inbred strains and their reciprocal hybrids. The effect of prior experience on defecation was more complex: Within the two inbred strains, prior experience had relatively little effect on the pattern of defecation; for the F₁ hybrids, however, prior experience led to a significant increase in defecation at most ages. It was suggested that the differential effect of test experience on open-field activity and defecation represents a separation of two components of open-field behavior, “exploration” and “emotionality.”     

Maternal food restriction: Effects on offspring behavior and development

Pregnant rats were placed on reduced food intake or remained on adequate diet during gestation and lactation. Offspring were cross-fostered to provide for independent experiences of prenatal and/or postnatal mother malnutrition. All offspring were placed on an ad lib diet at time of weaning. When evaluated in adulthood, offspring whose mother was food-deprived during the lactation period showed body weight deficits and increased errors on the Hebb-Williams maze as compared to controls. There were no observed effects of the prenatal deprivation.     

Effects of infantile handling on morphological development of the rat brain: An exploratory study

Rats were handled daily from day 2 to 11 after birth, inclusive. These animals and unhandled controls were injected on day 11 with a radioactively-labeled precursor of deoxyribonucleic acid (DNA) and killed either 6 hr, 3 or 30 days later. In a subsequent experiment, uninjected rats were likewise permitted to survive until 11, 14, 41, or 101 days of age. Brain weight measurements were taken in all animals, and the brains from the rats of the first experiment prepared for histology and autoradiography, and evaluated quantitatively. The following differences were established: (1) The brains of the handled rats were consistently lighter than controls at 11 and 14 days; (2) These differences were not associated with differences in body weight; (3) Planimetric measurements of sampled regions showed that brain weight differences were correlated with areal size differences; (4) Autoradiographic cell counting indicated that cell proliferation and the formation of new microneurons were higher after injection in the handled than unhandled rats; (5) No differences attributable to the treatment were obtained between relative areas occupied in cortex by perikarya and neuropil. We concluded that handling leads to prolongation of brain maturation and hypothesized that it represents environmentally-induced “infantilization.”     

Effects of mounts without intromission upon the behavior of female rats during the onset of estrogen-induced heat

The effects of pre-test mounting upon subsequent behavior of female rats was investigated using 40 ovariectomized females brought into heat with exogenous hormones. Half of the females were primed with 50 mounts by the males, and pairs of primed and non-primed females were tested to a 10-mount criterion. Intromission was prevented by vaginal masks. Pre-test mounting of non-receptive females decreased their subsequent rejection of the males. But rather than having a priming effect upon sexual receptivity, mounts without intromission decreased the probability and intensity of subsequent lordosis.     

Effects of environmental enrichment and paradoxical sleep deprivation on open-field behavior of amphetamine-treated mice

BACKGROUND: Environmental enrichment or paradoxical sleep deprivation (PSD) has been shown to modify some responses elicited by drugs of abuse. The aims of the present study were to examine the effects of environmental enrichment and PSD, conducted separately or in association, on open-field behavior elicited by amphetamine (AMP) in mice. METHODS: Male C57BL/6 mice were randomly assigned to live in either an enriched environmental condition (EC) or a standard environmental condition (SC) for 12 months since weaning. Some of the EC and SC mice were sleep deprived for 48 h, while others were maintained in their home-cages. Immediately after PSD or home-cage stay, the animals received an ip injection of saline, 2.5 mg/kg AMP or 5.0 mg/kg AMP. Fifteen minutes later, their open-field behavior was quantified. RESULTS: Whereas PSD enhanced total and peripheral locomotor activity of acutely AMP-treated mice, environmental enrichment presented only a trend toward enhancement. When PSD and environmental enrichment were combined, an increase in the total and peripheral locomotion frequencies of AMP-treated animals, similar to that observed after PSD, was revealed. In addition, PSD, environmental enrichment or their combination did not modify the effects of AMP on the other open-field behavioral parameters that were analyzed. CONCLUSION: The present findings demonstrate that some (but not all) of the behavioral effects caused by AMP acute administration can be similarly and specifically enhanced by both environmental enrichment and PSD in C57BL/6 mice.     

Intergenerational transmission of maternal behavior in rhesus macaques and its underlying mechanisms

Thirteen group-living rhesus macaque females that were crossfostered shortly after birth were followed longitudinally until they gave birth for the first time. Their maternal behavior was compared to the behavior of both their foster and their biological mothers, and analyzed in relation to the cerebrospinal fluid (CSF) concentrations of serotonin, dopamine, and norepinephrine metabolites (5-HIAA, HVA, and MHPG) measured in their second year of life. Crossfostered females were similar to their foster mothers in their rates of maternal rejection and grooming, whereas their contact-making behavior was more similar to that of their biological mothers. Crossfostered females with lower CSF concentrations of 5-HIAA exhibited higher rates of maternal rejection than females with higher CSF 5-HIAA. In a related article (Maestripieri et al., 2006), we reported that rhesus infants reared by highly rejecting mothers had lower CSF 5-HIAA in their first 3 years of life. Taken together, these findings suggest that early social experience and experience-related long-term changes in serotonergic function may play a role in the intergenerational transmission of maternal rejection from mothers to daughters.     

Comparison of the effects of early handling and early deprivation on maternal care in the rat

It has been reported in the rat that postnatal manipulations can induce robust and persistent effects on offspring neurobiology and behavior, mediated in part via effects on maternal care. There have, however, been few studies of the effects of postnatal manipulations on maternal care. Here, we describe and compare the effects on maternal behavior on postnatal days 1-12 of two manipulations, early handling (EH, 15-min isolation per day) and early deprivation (ED, 4-hr isolation per day), relative to our normal postnatal husbandry procedure. Maternal behavior was measured at five time points across the dark phase of the reversed L:D cycle. EH yielded an increase in arched-back nursing across several time points but did not affect any other behavior. ED stimulated a bout of maternal behavior such that licking and arched-back nursing were increased at the time of dam-litter reunion, although not at any other time point. Neither EH nor ED affected weaning weight significantly. Importantly, within-treatment variation was high relative to these between-treatment effects.     

Neonatal handling induces deficits in infant mother preference and adult partner preference

Neonatal handling is an experimental procedure used to understand how early‐life adversity can negatively affect neurobehavioral development and place animals on a pathway to pathology. Decreased preference for the maternal odor during infancy is one of many behavioral deficits induced by neonatal handling. Here, we hypothesize that deficits in maternal odor preference may interfere with partner preference in the adult. To test this hypothesis, we assessed infant maternal odor preference and adult partner preference in different reproductive stages in both male and female rats that received neonatal handling. Our results indicate that only neonatally handled females present deficits in maternal odor preference during infancy, but both male and females present deficits in adult partner preference. However, sexual experience was effective in rescuing partner preference deficits in males. These results indicate that, considering infant and adult social interactions, females are more susceptible to the effects of neonatal handling than males. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 496–507, 2013     

Temperature reduction in neonatal mice: Effects on later behavior

The effects of body temperature reduction in neonatal C57BL/6J mice were studied in 2 experiments. Experiment I investigated the development of the thermoregulatory response of mice from 1 to 15 days of age in their nest and in an ambient environment of 22°C. The experimental conditions could then be specified to produce body temperature reduction of either 5 or 10°C for 10 min from day 1 through 15. In Experiment 2, effects of these body temperature reductions at day 1 to 5, 6 to 10, or 11 to 15 on subsequent behavior at 30 and 70 days of age were studied. Three control groups (handled, non-temperature maintained; handled, temperature maintained; and nonhandled) were treated at the same age periods. Behavioral tests were open field, water runway, water maze (preference) and single-alternation problem, and water submersion. No consistent behavioral effects could be attributed to body temperature reduction or to age at treatment in infancy. Mice receiving body temperature reduction of 5 and 10°C, or handling (with or without body temperature reduction) behaved differently from nontreated subjects on latency and activity measures in an open field; on the latency measure in the water maze (preference) test; on the errors and days to criterion measures in the single-alternation water maze; and in time-to-submersion in water. The behavioral alterations of the treated groups could be interpreted to represent reduced emotionality, and improved performance and learning ability resulting from the neonatal experiences.     

Developmental environment: variables important for later learning and changes in cholinergic activity

Environmental experience of developing rats was manipulated in two ways. These were (1) providing increments in amount of visual stimulation vs. increased variety of novelty of visual stimulation, and (2) informal experience vs. formal training in discriminating between the given stimuli. At the conclusion of the developmental treatment an index of performance change was obtained by testing discrimination learning on a Lashley Jumping Stand. Effects on the cholinergic system, specifically, acetylcholinesterase (AChE) and cholinesterase (ChE) activities, were also examined. Increments in variety of stimulation, but not increases in amount, were found to contribute significantly to observed differences in AChE and ChE activity and in learning performance. Formal training in addition to enriched informal experience added little to either the biochemical effects or to the observed improvement in performance on the relevant learning task.