Developmental Lead Exposure in Rats Causes Sex-Dependent Changes in Neurobiological and Anxiety-Like Behaviors that Are Improved by Taurine Co-treatment.

Lead (Pb2+) is a developmental neurotoxicant that causes alterations in the brain's excitation-to-inhibition (E/I) balance by disrupting the development of the GABAergic systems. These GABAergic disruptions have persistent neurobiological and neurobehavioral structure-function relationships that can be examined using animal models of Pb2+ exposure. Further, taurine, a GABA-AR agonist, has been shown to offer neuroprotection against neurodevelopmental Pb2+ exposure and senescence. The present study evaluated the effects of Pb2+ exposure (i.e., at 150 ppm and 1,000 ppm doses) on Long Evans hooded rats during the perinatal period of development on locomotor activity in the open field (OF) and anxiety-like behaviors in the elevated plus maze (EPM). This was followed by an examination of brain mass using an encephalization quotient (EQ) and isotropic fractionation (ITF) of total cells and the number of neurons and non-neuronal cells in the prefrontal cortex, hippocampus, and diencephalon. The results suggest that neurodevelopmental Pb2+ exposure caused persistent anxiety-like behaviors in both the OF and EPM with associated changes in EQ, but not ITF-determined cell density. Further, taurine treatment was observed to compensate for Pb2+ exposure in the behavioral assessments although precise neurobiological mechanisms remain unknown. Thus, more work is required to evaluate the role of taurine and other anxiolytic compounds in the alleviation of neurotoxicant-induced neurobehavioral syndromes and their associated neurobiological correlates.

Challenges to the parental brain: Neuroethological and translational considerations.

Extending from research documenting adaptive parental responses in nonthreatening contexts, the influences of various neuroethological and physiological challenges on effective parenting responses are considered in the current review. In natural habitats, rodent family units are exposed to predators, compromised resources, and other environmental stressors that disrupt HPA axis functions. With the additional physiological demands associated with caring for offspring, alterations in stress-related neuroendocrine responsiveness contribute to adaptive responses in many challenging contexts. Some environmental contexts, however, such as restricted nesting resources, result in disrupted maternal responses that have a negative impact on offspring wellbeing. Additionally, parental dysregulation associated with exposure to environmental chemicals or pharmacological substances, also compromise maternal responses with effects that often extend to future generations. Continued preclinical and clinical research elucidating parental responses to various stressors and physiological disruptors is necessary to provide valuable translational information identifying threats to effective parenting outcomes.

Enriched Environment Exposure Enhances Social Interactions and Oxytocin Responsiveness in Male Long-Evans Rats.

Both social and physical stimuli contribute to the complexity of an animal's environment, influencing biobehavioral responses to subsequent challenges. In the current study, male Long-Evans rats were randomly assigned to an isolate (ISO), social control (SC) or social enriched (SE) group (n = 8 per group). The SC and SE conditions were group housed with the SE group exposed to physical enrichment stimuli that were natural as opposed to manufactured (e.g., hollowed out log instead of plastic hiding place). On three occasions during their 40-day enriched environment exposure, night/dark phase videos were obtained for 1 h during the early part of the dark phase. During this time, the SE animals exhibited significantly more social grooming with no differences between the SE and SC in the frequency of play or self-grooming bouts. Subsequently, all animals were assessed in social interaction and problem-solving escape tasks during the last week of the enriched environment exposure. SE rats exhibited increased digging bouts toward the restrained conspecific in the social interaction task whereas the other groups exhibited more escape responses. In the problem-solving task, SE animals exhibited a decreased latency to cross the barrier to escape from the predator odor (i.e., cat urine and fur). Neural analyses indicated increased oxytocin-immunoreactive (OT-ir) tissue in the SE supraoptic and paraventricular nuclei of the hypothalamus compared to the other groups. Interestingly, blood samples indicated lower peripheral corticosterone (CORT) and higher OT levels in the ISO animals when compared to the SC and SE animals, an effect retrospectively attributed to separation anxiety in the SE and SC animals in preparation for histology procedures. When the behavioral, neural and endocrine data were visualized as a multifaceted dataset via a multidimensional scaling analysis, however, an association between social enrichment and higher OT involvement was observed in the SE animals, as well as heightened stress responsivity in the ISO and SC groups. In sum, the SE animals exhibited a facilitation of social responses, problem-solving ability and OT immunoreactive responsiveness. These findings provide new information about the influences of both physical and social stimuli in dynamic and enriched environments.

Physiologic Correlates of Interactions between Adult Male and Immature Long-tailed Macaques (Macaca fascicularis).

Interactions between adult males and immature members of the same species are rare in most mammals; in contrast, an estimated 40% of primate species are characterized by an involvement of males in the social life of infants and juveniles. The proximate mechanisms of male-infant interactions are largely unstudied, and very few direct benefits for males have been proposed, especially in uniparental species in which the identity of the male parent is uncertain. In this study, we aimed to assess the relationship among behavioral and physiologic stress, health, and various affiliative behaviors initiated by adult males toward infants and juveniles in long-tailed macaques. We hypothesized that males that spent more time with infants and juveniles would have lower physiologic and social stress and better health than males with less interaction. We observed 2 troops of macaques with established social hierarchies (n = 18 in troop 1 and n = 8 in troop 2), each occupying a stable area within the enclosure, for more than 200 h. Fecal samples were used to assess cortisol levels as a measure of physiologic stress, and blood samples were collected to measure oxytocin levels as an index of social responsiveness. Our results indicated that male affiliative behavior directed toward immature animals was significantly higher in the troop characterized by more social conflicts; midranking males interacted more with infants than high- and low-ranking males in both troops. Furthermore, the DHEA:cortisol ratio, a physiologic index of resilience and coping, was positively correlated with males' affiliative responses, suggesting a neuroprotective role of male-infant interactions. In summary, our data support a proximate mechanism of alloparenting or paternal behavior in uniparental species. Interacting with infants and juveniles could provide an immediate neurobiologic benefit to adult males by facilitating adaptive coping responses to social tensions.

Neuroplasticity in the maternal hippocampus: Relation to cognition and effects of repeated stress.

This article is part of a Special Issue "Parental Care". It is becoming clear that the female brain has an inherent plasticity that is expressed during reproduction. The changes that occur benefit the offspring, which in turn secures the survival of the mother's genetic legacy. Thus, the onset of maternal motivation involves basic mechanisms from genetic expression profiles, to hormone release, to hormone-neuron interactions, all of which fundamentally change the neural architecture - and for a period of time that extends, interestingly, beyond the reproductive life of the female. Although multiple brain areas involved in maternal responses are discussed, this review focuses primarily on plasticity in the maternal hippocampus during pregnancy, the postpartum period and well into aging as it pertains to changes in cognition. In addition, the effects of prolonged and repeated stress on these dynamic responses are considered. The maternal brain is a marvel of directed change, extending into behaviors both obvious (infant-directed) and less obvious (predation, cognition). In sum, the far-reaching effects of reproduction on the female nervous system provide an opportunity to investigate neuroplasticity and behavioral flexibility in a natural mammalian model.

Brains in the city: Neurobiological effects of urbanization.

With a majority of humans now living in cities, strategic research is necessary to elucidate the impact of this evolutionarily unfamiliar habitat on neural functions and well-being. In this review, both rodent and human models are considered in the evaluation of the changing physical and social landscapes associated with urban dwellings. Animal models assessing increased exposure to artificial physical elements characteristic of urban settings, as well as exposure to unnatural sources of light for extended durations, are reviewed. In both cases, increased biomarkers of mental illnesses such as major depression have been observed. Additionally, applied human research emphasizing the emotional impact of environmental threats associated with urban habitats is considered. Subjects evaluated in an inner-city hospital reveal the impact of combined specific genetic vulnerabilities and heightened stress responses in the expression of posttraumatic stress disorder. Finally, algorithm-based models of cities have been developed utilizing population-level analyses to identify risk factors for psychiatric illness. Although complex, the use of multiple research approaches, as described herein, results in an enhanced understanding of urbanization and its far-reaching effects--confirming the importance of continued research directed toward the identification of putative risk factors associated with psychiatric illness in urban settings.

Parity modifies endocrine hormones in urine and problem-solving strategies of captive owl monkeys (Aotus spp.).

Parental behavior modifies neural, physiologic, and behavioral characteristics of both maternal and paternal mammals. These parenting-induced modifications extend to brain regions not typically associated with parental responses themselves but that enhance ancillary responses, such as foraging efficiency and predator avoidance. Here we hypothesized that male and female owl monkeys (Aotus spp.) with reproductive experience (RE) would demonstrate more adaptive ancillary behavioral and neuroendocrine responses than those of their nonRE counterparts. To assess cognitive skills and coping flexibility, we introduced a foraging strategy task, including a set of novel objects (coin holders) marked with different symbols representing different food rewards, to the animals. To assess endocrine responses, urine samples were assayed for cortisol and dehydroepiandrosterone (DHEA) levels and their ratios to determine physiologic measures of emotional regulation in RE and nonRE owl monkeys. Compared with nonRE monkeys, experienced parents had higher DHEA:cortisol ratios after exposure to habituation training and on the first day of testing in the foraging task. Both hormones play critical roles in the stress response and coping mechanisms, and a high DHEA:cortisol ratio usually indicates increased coping skills. In addition, RE monkeys exhibited more efficient foraging responses (by 4-fold) than did the nonRE mating pairs. We conclude that RE modifies relevant behavioral and hormonal responses of both maternal and paternal owl monkeys exposed to a challenging cognitive paradigm. Corroborating previous research demonstrating adaptive modifications in foraging efficiency and emotional responses in reproductively experienced rodents, the current results extend these findings to a monogamous primate species.

The mother as hunter: significant reduction in foraging costs through enhancements of predation in maternal rats.

In previous laboratory investigations, we have identified enhanced cognition and reduced stress in parous rats, which are likely adaptations in mothers needing to efficiently exploit resources to maintain, protect and provision their immature offspring. Here, in a series of seven behavioral tests on rats, we examined a natural interface between cognition and resource gathering: predation. Experiment 1 compared predatory behavior (toward crickets) in age-matched nulliparous mothers (NULLs) and postpartum lactating mothers (LACTs), revealing a highly significant enhancement of predation in LACT females (mean = -65s in LACTs, vs. -270s in NULLs). Experiment 2 examined the possibility that LACTs, given their increased metabolic rate, were hungrier, and thus more motivated to hunt; doubling the length of time of food deprivation in NULLs did not decrease their predatory latencies. Experiments 3-5, which examined sensory regulation of the effect, indicated that olfaction (anosmia), audition (blockade with white noise), and somatosensation (trimming the vibrissae) appear to play little role in the behavioral enhancement observed in the LACTs; Experiment 6 examined the possibility that visual augmentations may facilitate the improvements in predation; testing LACTs in a 0-lux environment eliminated the behavioral advantage (increasing their latencies from -65s to -212s), which suggests that temporary augmentation to the visual system may be important, and with hormone-neural alterations therein a likely candidate for further study. In contrast, testing NULLS in the 0-lux environment had the opposite effect, reducing their latency to catch the cricket (from -270s to -200s). Finally, Experiment 7 examined the development of predatory behavior in Early-pregnant (PREG), Mid-PREG, and Late-PREG females. Here, we observed a significant enhancement of predation in Mid-PREG and Late-PREG females--at a time when maternity-associated bodily changes would be expected to diminish predation ability--relative to NULLs. Therefore, as with the increasing reports of enhancements to the maternal brain, it is apparent that meaningful behavioral adaptations occur that likewise promote the survival of the mother and her infants at a crucial stage of their lives.

Contingency-based emotional resilience: effort-based reward training and flexible coping lead to adaptive responses to uncertainty in male rats.

Emotional resilience enhances an animal's ability to maintain physiological allostasis and adaptive responses in the midst of challenges ranging from cognitive uncertainty to chronic stress. In the current study, neurobiological factors related to strategic responses to uncertainty produced by prediction errors were investigated by initially profiling male rats as passive, active or flexible copers (n = 12 each group) and assigning to either a contingency-trained or non-contingency trained group. Animals were subsequently trained in a spatial learning task so that problem solving strategies in the final probe task, as well-various biomarkers of brain activation and plasticity in brain areas associated with cognition and emotional regulation, could be assessed. Additionally, fecal samples were collected to further determine markers of stress responsivity and emotional resilience. Results indicated that contingency-trained rats exhibited more adaptive responses in the probe trial (e.g., fewer interrupted grooming sequences and more targeted search strategies) than the noncontingent-trained rats; additionally, increased DHEA/CORT ratios were observed in the contingent-trained animals. Diminished activation of the habenula (i.e., fos-immunoreactivity) was correlated with resilience factors such as increased levels of DHEA metabolites during cognitive training. Of the three coping profiles, flexible copers exhibited enhanced neuroplasticity (i.e., increased dentate gyrus doublecortin-immunoreactivity) compared to the more consistently responding active and passive copers. Thus, in the current study, contingency training via effort-based reward (EBR) training, enhanced by a flexible coping style, provided neurobiological resilience and adaptive responses to prediction errors in the final probe trial. These findings have implications for psychiatric illnesses that are influenced by altered stress responses and decision-making abilities (e.g., depression).

Effort-Based Reward (EBR) training enhances neurobiological efficiency in a problem-solving task: insights for depression therapies.

Effort-Based Reward (EBR) training strengthens associations between effort and rewards, leading to increased persistence in an unsolvable task when compared to control animals. EBR training involves placing animals in a test apparatus in which they are trained to dig in mounds to retrieve froot loop rewards (contingent group); these animals are compared to control animals that are given the same number of rewards, regardless of expended effort (noncontingent group). In the current study, the effect of EBR training on performance in a spatial task (Dry Land Maze) was explored to determine cognitive resilience during behavioral testing. Additionally, animals received BrdU injections during training to assess the role of neurogenesis on subsequent behavioral performance. Following the probe test, animals were perfused so that fos-immunoreactive (ir) cells in the hippocampus and cortical areas could be assessed. Behavioral results indicated that contingent rats were approximately 50% more efficient in locating and interacting with the previous baited well during the probe test than noncontingent animals, recruiting approximately 20% less c-fos ir-cells in the insular cortex, retrosplenial cortex, and dentate gyrus. A multidimensional scaling analysis grouped noncontingent animals together in a quadrant characterized by high latencies to find the previous baited well and higher ir-cell activation in the aforementioned areas. Thus, our data support the hypothesis that the EBR training enhances both cognitive functioning and emotional regulation during challenging events. Considering the ongoing controversy about the efficacy of pharmacological interventions in treating depression, the EBR model provides a valuable alternative for the investigation of the neurobiology of mood disorders.

Reproductive experience facilitates recovery from kainic acid-induced neural insult in female Long-Evans rats.

The hormones of pregnancy and lactation (e.g., estrogen, progesterone, and oxytocin) have been shown to modulate learning, memory, and the restructuring of brain areas not traditionally associated with maternal behavior. Given the impact of reproductive experience on plasticity of brain areas such as the hippocampus, kainic acid (KA) was used in the current study to induce hippocampal-specific neurotoxic insult in adult multiparous and virgin Long-Evans rats. In Experiment I, Fluoro-Jade B, an indicant of degenerating cells, revealed significant neuronal damage in KA-treated hippocampi at 16 h post-injection in both maternal and virgin rats. In Experiment II, maternal and virgin rats were assessed in spatial and novel object preference tasks to determine the effects of KA on subsequent behavioral and cognitive responses. Twenty-four hours post injection, saline maternal animals exhibited superior memory in a spatial task. Further, maternal saline-injected rats were more similar to maternal KA-injected rats than both the virgin groups. Forty-eight hours following the KA or saline injection, compared to virgins, maternal animals demonstrated enhanced memory in the novel object memory test, regardless of type of injection. Further, neurobiological assessments in Experiment II indicated that virgin KA exposed rats had significantly more glial fibrillary acidic protein (GFAP)-immunoreactivity in the hippocampus, suggesting that they were in an earlier stage of neural recovery compared to maternal animals or, alternatively, may have exhibited more trauma than maternal animals. Together, these data suggest that the previously reported plasticity of the maternal brain may facilitate neural and behavioral recovery from neural insults.

The parental brain: transformations and adaptations.

Few evolutionary transformations rival the complex neurobiological modifications accompanying the mammalian transition to parenthood. Research conducted primarily in maternal rodents highlights the engagement of multiple areas of the brain to initiate and maintain interest in resource-depleting vulnerable pups throughout lactation. Interestingly, many modifications marking the transition to motherhood result in adaptive response options that persist well beyond the weaning of pups; specifically, adaptations such as cognitive flexibility, emotional regulation and enhanced social attentiveness coincide with the parenthood transition and have emerged as defining characteristics of the most adaptive mammalian species. The paternal brain also results in interesting modifications that, in some biparental species, mimic the effects observed in females. Taken together, research suggests that the designation of "parent" is less of a categorical variable and more of a continuous variable, with the quality of nurturing responses directed toward offspring influenced by many factors such as predisposed sensitivity to reproductive hormones, nature and duration of exposure to offspring, number of reproductive experiences, adequate resources, and composition of the social environment. Indeed, the transition from an animal focused on self-preservation to one that is responsive to the needs of other animals, and the accompanying increases in reproductive fitness, represent a significant evolutionary transition, or upgrade of sorts, leading to a more diverse array of response options to meet the challenging demands of changing environmental and social terrains.

Behavioral training and predisposed coping strategies interact to influence resilience in male Long-Evans rats: implications for depression.

Effective coping strategies and adaptive behavioral training build resilience against stress-induced pathology. Both predisposed and acquired coping strategies were investigated in rats to determine their impact on stress responsiveness and emotional resilience. Male Long-Evans rats were assigned to one of the three coping groups: passive, active, or variable copers. Rats were then randomly assigned to either an effort-based reward (EBR) contingent training group or a non-contingent training group. Following EBR training, rats were tested in appetitive and stressful challenge tasks. Physiological responses included changes in fecal corticosterone and dehydroepiandrosterone (DHEA) metabolites as well as neuropeptide Y (NPY)-immunoreactivity in the hippocampus and amygdala. Regardless of a rat's predisposed coping strategy, EBR rats persisted longer than non-contingent rats in the appetitive problem-solving task. Furthermore, training and coping styles interacted to yield the seemingly most adaptive DHEA/corticosterone ratios in the EBR-trained variable copers. Regardless of training group, variable copers exhibited increased NPY-immunoreactivity in the CA1 region.

Alterations of sex-typical microanatomy: prenatal stress modifies the structure of medial preoptic area neurons in rats.

Prenatal stress disrupts normal sexual differentiation and behavior with concomitant alterations in brain development; however, its effects on the cytoarchitecture of neurons in the sexually dimorphic medial preoptic area (mPOA) of the hypothalamus is not known. Morphometric analysis of the mPOA of adult rats showed sex differences as neurons from control females had significantly greater numbers of basal dendritic branches and cumulative basal dendritic length as compared to control male neurons. Prenatal stress significantly altered these sexual dimorphisms, as prenatally stressed (P-S) males had increased measures of cell body area, perimeter, cumulative basal dendritic length, and branch point numbers as compared to control males. Prenatal stress also altered the cytoarchitecture in the female mPOA neurons as P-S female neurons had significantly greater measures for primary dendritic branch number and a trend towards significance for several additional measures as compared to control females. Therefore, there are significant effects of both sex and prenatal stress on neuronal architecture in the mPOA that may help to explain the well-documented alterations in reproductive behaviors observed in P-S animals.

Using a comparative species approach to investigate the neurobiology of paternal responses.

A goal of behavioral neuroscience is to identify underlying neurobiological factors that regulate specific behaviors. Using animal models to accomplish this goal, many methodological strategies require invasive techniques to manipulate the intensity of the behavior of interest (e.g., lesion methods, pharmacological manipulations, microdialysis techniques, genetically-engineered animal models). The utilization of a comparative species approach allows researchers to take advantage of naturally occurring differences in response strategies existing in closely related species. In our lab, we use two species of the Peromyscus genus that differ in paternal responses. The male California deer mouse (Peromyscus californicus) exhibits the same parental responses as the female whereas its cousin, the common deer mouse (Peromyscus maniculatus) exhibits virtually no nurturing/parental responses in the presence of pups. Of specific interest in this article is an exploration of the neurobiological factors associated with the affiliative social responses exhibited by the paternal California deer mouse. Because the behavioral neuroscience approach is multifaceted, the following key components of the study will be briefly addressed: the identification of appropriate species for this type of research; data collection for behavioral analysis; preparation and sectioning of the brains; basic steps involved in immunocytochemistry for the quantification of vasopressin-immunoreactivity; the use of neuroimaging software to quantify the brain tissue; the use of a microsequencing video analysis to score behavior and, finally, the appropriate statistical analyses to provide the most informed interpretations of the research findings.

Paternal experience and stress responses in California mice (Peromyscus californicus).

Paternal behavior greatly affects the survival, social development, and cognitive development of infants. Nevertheless, little research has been done to assess how paternal experience modifies the behavioral characteristics of fathers, including fear and stress responses to a novel environment. We investigated long-term behavioral and physiologic effects of parental experience in mice (Peromyscus californicus) and how this response activates the hypothalamic-pituitary-adrenal axis (as measured by corticosterone and dehydroepiandrosterone [DHEA] levels) and interacts with anxiety-related behaviors. Three groups of adult males were tested--fathers exposed to pups, virgins exposed to pups, and virgins never exposed to pups--in 2 environments designed to elicit anxiety response: an open field with a novel object placed in the center and a closed cage containing a sample of a component of fox feces. Behavioral responses were measured by using traditional methods (duration and frequency) and behavioral-chain sequences. Results indicated that paternal experience significantly modifies a male mouse's behavioral and physiologic responses to stress-provoking stimuli. Compared with inexperienced male mice, experienced male mice had a significant decrease in the occurrence of incomplete behavioral chains during the exposure to the novel object, an index of reduced stress. Further, even moderate pup exposure induced behavioral modifications in virgin male mice. These behavioral responses were correlated with changes in corticosterone and DHEA levels. Together, these data provide evidence that interactions between male mice and offspring may have mutually beneficial long-term behavioral and physiologic effects.

Characteristic neurobiological patterns differentiate paternal responsiveness in two Peromyscus species.

Rodent paternal models provide unique opportunities to investigate the emergence of affiliative social behavior in mammals. Using biparental and uniparental Peromyscus species (californicus and maniculatus, respectively) we assessed paternal responsiveness by exposing males to biological offspring, unrelated conspecific pups, or familiar brothers following a 24-hour separation. The putative paternal circuit we investigated included brain areas involved in fear/anxiety [cingulate cortex (Cg), medial amygdala (MeA), paraventricular nucleus of the hypothalamus (PVN), and lateral septum (LS)], parental motivation [medial preoptic area (MPOA)], learning/behavioral plasticity (hippocampus), olfaction [pyriform cortex (PC)], and social rewards (nucleus accumbens). Paternal experience in californicus males reduced fos immunoreactivity (ir) in several fear/anxiety areas; additionally, all californicus groups exhibited decreased fos-ir in the PC. Enhanced arginine vasopressin (AVP) and oxytocin (OT)-ir cell bodies and fibers, as well as increased neuronal restructuring in the hippocampus, were also observed in californicus mice. Multidimensional scaling analyses revealed distinct brain activation profiles differentiating californicus biological fathers, pup-exposed virgins, and pup-naïve virgins. Specifically, associations among MPOA fos, CA1 fos, dentate gyrus GFAP, CA2 nestin-, and PVN OT-ir characterized biological fathers; LS fos-, Cg fos-, and AVP-ir characterized pup-exposed virgins, and PC-, PVN-, and MeA fos-ir characterized pup-naïve virgins. Thus, whereas fear/anxiety areas characterized pup-naïve males, neurobiological factors involved in more diverse functions such as learning, motivation, and nurturing responses characterized fatherhood in biparental californicus mice. Less distinct paternal-dependent activation patterns were observed in uniparental maniculatus mice. These data suggest that dual neurobiological circuits, leading to the inhibition of social-dependent anxiety as well as the activation of affiliative responses, characterize the transition from nonpaternal to paternal status in californicus mice.

Neurobiological constituents of active, passive, and variable coping strategies in rats: integration of regional brain neuropeptide Y levels and cardiovascular responses.

Effective coping strategies build resilience against stress-induced pathology. In the current study, young male rats were categorized as active, passive, or variable copers by observing their responses to being gently restrained on their backs (i.e., the back-test). The rats were subsequently exposed to chronic unpredictable stress, which included several ethologically relevant stressors such as predator odors and calls, for approximately three weeks. During this time, the variable copers, defined as rats that demonstrated a variable as opposed to a rigid response to stress, exhibited more seemingly adaptive responsiveness in three successive forced swim tests than the more consistently responding passive and active copers. This behavioral flexibility was accompanied by increased neuropeptide Y-immunoreactivity in the bed nucleus of the stria terminalis (BNST) and the amygdala and increased fos-immunoreactivity in the BNST. Additionally, the alterations in fecal corticosteroid levels and cardiovascular measures (systolic blood pressure and tail blood volume) between baseline and stress conditions differed according to coping strategy. Factor analysis indicates that variable copers were characterized by a distinct cardiovascular and neural response to the stress exposure. These results suggest that this animal coping model may be useful in discerning the adaptive nature of particular response strategies in the face of environmental exigencies.

Fecal dehydroepiandrosterone (DHEA) immunoreactivity as a noninvasive index of circulating DHEA activity in young male laboratory rats.

Evidence suggests that dehydroepiandrosterone (DHEA) plays a key role in stress and coping responses. Fecal sampling permits assessment of hormone-behavior interactions reliably and effectively, but no previous study has compared circadian- or stress-dependent alterations between serum DHEA and its fecal metabolites. In the current study, young (28 d of age) male rats were assigned to either an experimental (n = 6) or control (n = 6) group. Rats in the experimental group were exposed to a forced swim test to assess their behavioral and physiologic response to an environmental stressor; blood samples were drawn before the test (baseline), immediately after the test, and at 2 later time points. Only fecal samples were collected from control animals. Fecal DHEA and corticosterone metabolites were monitored in all animals for 24 h. DHEA metabolites in control rats exhibited significant diurnal variation, showing a similar temporal pattern as that of corticosterone metabolites. In addition, fecal and serum DHEA levels were highly correlated. Significant peaks in both DHEA and corticosterone metabolite levels were detected. These data suggest that measures of fecal DHEA can provide a complementary, noninvasive method of assessing adrenal gland function in rats.