A hamster model for stress-induced weight gain.

This review addresses the translational relevance of animal models of stress and their effects on body weight. In humans, stress, whether chronic or acute, has often been associated with increased food intake and weight gain. In view of the current obesity epidemic, this phenomenon is especially relevant. Such observations contrast with reports with commonly used laboratory animals, especially rats and mice. In these species, it is common to find individuals gaining less weight under stress, even with potent social stressors. However, there are laboratory species that present increased appetite and weight gain under stress, such as golden hamsters. Furthermore, these animals also include metabolic and behavioral similarities with humans, including hoarding behavior which is also enhanced under stress. Consequently, we propose that our comparative perspective provides useful insights for future research on the development of obesity in humans as a consequence of chronic stress exposure.

Lifelong enhancement of body mass from adolescent stress in male hamsters.

In hamsters, exposure to stress in adulthood causes increased body weight. We addressed how social stress during puberty would impact food intake and body weight. Stressed hamsters started gaining significantly more weight than controls after only two days of stress exposure. Over a two-week period, stressed subjects gained 10% more weight and consumed more food than controls. At the end of the stress period, stressed hamsters collected nearly twice as many palatable sugar pellets from an arena than controls. Stressed subjects presented 15-20% more body fat in mesenteric, inguinal, and retroperitoneal fat pads. In order to assess the duration of these effects, we analyzed data from previous studies keeping hamsters for over two months past the stress period in puberty. Our analysis shows that stressed hamsters stopped gaining more weight after the stress period, but their body weights remained elevated for over two months, consistently weighing 10% more than their non-stressed counterparts. We also analyzed conditioning training data collected after the period of stress in late puberty and early adulthood (P56 to P70) that was part of the original studies. Training consisted of lever pressing for palatable food rewards. At these times, previously stressed hamsters retrieved similar numbers of food pellets from the conditioning chambers, suggesting no difference in appetite after the stress period. These data showing a long-lasting effect of stress on body weight may be relevant to studies on the ontogeny of lifelong obesity.

Early stress and waiting to respond versus waiting to receive.

Chronic social stress in early puberty results in enhanced impulsive action-in particular, decreased action inhibition. We address possible effects of early stress on the capacity to wait to respond, the other form of impulsive action. Male golden hamsters were exposed daily to aggressive adults from postnatal Day 28 to Day 42. Later in adulthood, animals were trained in a variable delay to respond task to nose-poke into a lit opening that triggered the delivery of food pellet rewards in response to a house light. During testing, we introduced random and varying delays between the house light presentation and illumination in the openings and examined premature nose-poking responses as an indicator of impulsive action. As delays grew longer, animals performed more premature responses. However, previously stressed animals were 25% less likely to perform such actions by the longest delay. As a control for this experiment, we conducted a separate study in which we introduced varying delays between the nose-poking response in the lit openings and the delivery of the reward. In this case, there were no significant differences between groups in repeated nose-poking after a correct response (repetitive responses). In summary, early stress has differential effects in response to introduction of delays in conditioning procedures: enhanced tolerance to delays between conditioning cues but no effect on responses when rewards are delayed. These studies confirm that early stress impacts the maturation of the neural systems mediating impulsive responses and provide a new perspective on the neuropsychology of waiting. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Social stress in early puberty has long-term impacts on impulsive action.

In hamsters, individuals attacked by adults during puberty become aggressive adults. Perhaps, enhanced aggression observed as repeated attacks toward opponents is associated with a lack of impulse control. We examined impulsive action in male golden hamsters exposed daily to aggressive adults from postnatal Day 28 to 42. These animals were trained in conditioning chambers and tested during adulthood in a go-no-go task addressing action inhibition. Overall, previously stressed hamsters were less likely to inhibit a conditioned lever pressing response during no-go trials. Because this effect could be the result of an extinction impairment, additional animals were tested to evaluate their response to omission of reward associated with conditioned lever pressing. In this experiment, all animals were equally capable of inhibiting their conditioned response. The capacity to inhibit a conditioned response was further addressed by testing responses to a 60-s reward delay after lever pressing. In this case, previously stressed animals were faster to inhibit lever pressing and stopped showing a preference for the proximity of the lever. These studies show selective condition-dependent effects on lever pressing activity and support the possibility that stress in early puberty enhances impulsive action in adulthood. These experiments may be relevant to the study of mental disorders associated with early trauma in humans. (PsycINFO Database Record

Chronic social stress in puberty alters appetitive male sexual behavior and neural metabolic activity.

Repeated social subjugation in early puberty lowers testosterone levels. We used hamsters to investigate the effects of social subjugation on male sexual behavior and metabolic activity within neural systems controlling social and motivational behaviors. Subjugated animals were exposed daily to aggressive adult males in early puberty for postnatal days 28 to 42, while control animals were placed in empty clean cages. On postnatal day 45, they were tested for male sexual behavior in the presence of receptive female. Alternatively, they were tested for mate choice after placement at the base of a Y-maze containing a sexually receptive female in one tip of the maze and an ovariectomized one on the other. Social subjugation did not affect the capacity to mate with receptive females. Although control animals were fast to approach females and preferred ovariectomized individuals, subjugated animals stayed away from them and showed no preference. Cytochrome oxidase activity was reduced within the preoptic area and ventral tegmental area in subjugated hamsters. In addition, the correlation of metabolic activity of these areas with the bed nucleus of the stria terminalis and anterior parietal cortex changed significantly from positive in controls to negative in subjugated animals. These data show that at mid-puberty, while male hamsters are capable of mating, their appetitive sexual behavior is not fully mature and this aspect of male sexual behavior is responsive to social subjugation. Furthermore, metabolic activity and coordination of activity in brain areas related to sexual behavior and motivation were altered by social subjugation.

Contrasting hippocampal and amygdalar expression of genes related to neural plasticity during escape from social aggression.

Social subjugation has widespread consequences affecting behavior and underlying neural systems. We hypothesized that individual differences in stress responsiveness were associated with differential expression of neurotrophin associated genes within the hippocampus and amygdala. To do this we examined the brains of hamsters placed in resident/intruder interactions, modified by the opportunity to escape from aggression. In the amygdala, aggressive social interaction stimulated increased BDNF receptor TrK(B) mRNA levels regardless of the ability to escape the aggressor. In contrast, the availability of escape limited the elevation of GluR(1) AMPA subunit mRNA. In the hippocampal CA(1), the glucocorticoid stress hormone, cortisol, was negatively correlated with BDNF and TrK(B) gene expression, but showed a positive correlation with BDNF expression in the DG. Latency to escape the aggressor was also negatively correlated with CA(1) BDNF expression. In contrast, the relationship between amygdalar TrK(B) and GluR(1) was positive with respect to escape latency. These results suggest that an interplay of stress and neurotrophic systems influences learned escape behavior. Animals which escape faster seem to have a more robust neurotrophic profile in the hippocampus, with the opposite of this pattern in the amygdala. We propose that changes in the equilibrium of hippocampal and amygdalar learning result in differing behavioral stress coping choices.

Developmental predictors of an impulsive-aggressive phenotype.

In hamsters, individual differences in offensive aggression are associated with impulsive choice, leading to the characterization of a distinct impulsive-aggressive phenotype. This study had two goals: to determine the developmental trajectory of the maturation of this phenotype and to address its parental lineage. Interestingly, individuals most aggressive as adults were less likely to attack in early puberty. However, looking at the transition of agonistic behavior from play fighting to adult aggression, impulsive-aggressive individuals were less likely to engage in play fighting attacks and more likely to engage in more mature agonistic behavior. Additionally, parental lineages were compared for the aggressive responses expressed by their adult offspring. Most impulsive-aggressive individuals were offspring of few select males, which were more likely to produce this phenotype, without an association with females or specific litters. These findings identify an abnormal and accelerated development of agonistic behavior in impulsive-aggressive individuals and a likelihood of heritability.

Differential responses to serotonin receptor ligands in an impulsive-aggressive phenotype.

Offensive aggression in golden hamsters is inhibited by 5-hydroxytryptamine (5-HT)1A receptors and facilitated by 5-HT3 receptor activation. As such, we sought to determine whether these receptors function similarly between animals expressing an impulsive-aggressive phenotype, as compared to normal animals. Animals were screened for aggressive and impulsive choice behaviors and categorized into Low-Aggression (L-Agg) and High-Aggression (H-Agg) groups, and then tested for behavior under effective doses of 5-HT1A receptor agonist 8-hydroxy-N, N-dipropyl-2-aminotetralin (DPAT; 0.1 mg/kg and 0.3 mg/kg) or 5-HT3 receptor antagonist tropisetron (0.3 mg/kg) treatment. Low-dose DPAT treatment inhibited both behaviors in H-Agg animals, however yielding more modest effects in L-Agg animals; while high-dose DPAT effects were confounded by side effects on locomotion. Tropisetron, on the other hand, had differential effects between groups, as aggression and impulsive choice were both inhibited in H-Agg animals, while enhanced in L-Agg individuals. In addition, while the effects of the 5-HT1A receptor were limited, the broad effects of 5-HT3 receptor included repetitive and impulsive elements of behavior, pointing to the importance of the receptor's role in the modulation of these particular aspects within the phenotype.

The cortisol response during physiological sexual arousal in adult women with a history of childhood sexual abuse.

Many women with a history of childhood sexual abuse (CSA) experience difficulties becoming sexually aroused. This study measured cortisol and physiological sexual arousal during exposure to sexual stimuli in women with and without a history of CSA. Childhood sexual abuse survivors showed a smaller decrease in cortisol during sexual arousal than the nonsexually abused, control group potentially due to an increase in cortisol in some of the participants in the CSA group. Physiological sexual arousal was weaker in CSA survivors compared to women with no history of sexual abuse and posttraumatic stress disorder symptoms showed characteristics consistent with mediation for the relationship between a history of CSA and inhibited sexual arousal responses.

Serotonin 5-HT1A and 5-HT3 receptors in an impulsive-aggressive phenotype.

In adult male hamsters, individual differences in offensive aggression are correlated with differences in impulsive choice and decreased serotonin (5-HT) innervation. As serotonin 1A (5-HT1A) receptors participate in the inhibition of aggression, whereas 5-HT3 receptor activation facilitates aggression, the authors hypothesized that differences in their expression are associated with differences in behavior. The authors confirmed previous behavioral associations, using a delay-discounting paradigm with various delays, as high-aggression (H-Agg) hamsters preferred the immediate-reward lever over the delayed-reward lever under most delays, compared with low-aggression (L-Agg) hamsters. Although the authors observed a greater density of 5-HT1A receptor immunoreactivity in H-Agg hamsters within several areas, it appears to be related to a lack of serotonin release, as supported by further observations of decreased immunoreactive perikarya and 5-HT1A receptors in fluoxetine-treated hamsters. Also, 5-HT3 receptor density was greater in H-Agg hamsters within select areas. The data indicate a convergence of impulsive and aggressive characteristics to one phenotype that is associated with various aspects of serotonin function, such as serotonin release and differential expression of 5-HT1A and 5-HT3 receptors.

Vasopressin facilitates play fighting in juvenile golden hamsters.

Vasopressin facilitates aggression in adult hamsters. Whether this neuropeptide has a similar role in play fighting remains unknown. The goal of the present study was to identify whether vasopressin controls play fighting in juvenile golden hamsters as well. Juvenile male golden hamsters were tested for play fighting after microinjections of a vasopressin V1A-receptor antagonist, Manning compound, either 0, 9, or 90 microM, into the anterior hypothalamus. The treatment selectively inhibited offensive aspects of play fighting in experimental animals. Attack frequencies were significantly decreased by both doses of Manning compound. In addition, the high dose of the receptor antagonist increased attack latencies, decreased bite frequencies, and decreased the averaged number of attacks per contact bout. Together, these results show that vasopressin controls offensive behaviors throughout development from play fighting in juveniles to aggression in adults.

Physiological stress response of young adults exposed to bullying during adolescence.

Peer victimization in the form of bullying is a chronic social stressor experienced by many humans during development. Exposure to bullying has been associated with a variety of mental disorders, such as anxiety and depression. Participants pre-selected for the presence or absence of a history of being bullied were brought into a laboratory and placed in a stressful situation. Blood pressure, heart rate, and salivary cortisol levels were measured before the introduction of the stressor (Time 1), at the end of the stressor (Time 2), and after its removal (Time 3). Men with a history of exposure to frequent bullying showed blunted blood pressure responses at Time 2 compared to control men. Bullied and Non-bullied women did not show any differences in any of the measures. Men and women in both groups showed an increase in heart rate in response to the stressor. There were no significant differences in salivary cortisol levels between Bullied and Non-bullied participants. However, salivary cortisol levels and systolic blood pressure were lower in Bullied male participants who reported having no feelings of anger about their experience compared to controls and those who did report anger. These data show altered sympathetic responses to stress in men with a history of victimization as well as suggesting long-term effects on the HPA axis in the most affected individuals.

Stress, aggression, and puberty: neuroendocrine correlates of the development of agonistic behavior in golden hamsters.

During puberty, agonistic behaviors undergo significant transitions. In golden hamsters, puberty is marked by a transition from play fighting to adult aggression. During early puberty, male golden hamsters perform play-fighting attacks. This response type is gradually replaced by adult attacks over the course of puberty. Interestingly, this behavioral transition does not appear to be controlled by changes in gonadal steroids. Instead, the shift from play fighting to adult aggression in male golden hamsters is driven by pubertal changes in glucocorticoid levels. Specifically, the transition from play fighting to adult aggression coincides with developmental increases in glucocorticoid levels, and external manipulations such as social stress or treatment with corticosteroid receptor agonists accelerate this behavioral shift. Moreover, the consequences of social stress differ greatly between juvenile and adult male golden hamsters. Although a single defeat during adulthood causes severe and long lasting behavioral and neuroendocrine consequences, socially subjugated juveniles show only transient behavioral effects. As such, it is likely that pubertal changes in the HPA axis are not only linked to the maturation of offensive responses but also determine the consequences of social stress. Combined, these studies in golden hamsters provide a novel mechanism for the development of agonistic behavior and suggest that age related differences in behavioral plasticity are mediated by the development of the HPA axis.

Sexual experience modulates neuronal activity in male Japanese quail.

After an initial increase, repeated exposure to a particular stimulus or familiarity with an event results in lower immediate early gene expression levels in relevant brain structures. We predicted that similar effects would occur in Japanese quail after repeated sexual experience within brain areas involved in sexual behavior, namely, the medial preoptic nucleus (POM), the bed nucleus of stria terminalis (BST), and the nucleus taeniae of the amygdala (TnA), an avian homolog of medial amygdala. High experience subjects copulated with a female once on each of 16 consecutive days, whereas low experience subjects were allowed to copulate either once or twice. Control subjects were never exposed to a female. High experience subjects were faster to initiate sexual interaction, performed more cloacal contacts, and completed each cloacal contact faster than low experience subjects. Low experience subjects showed an increase in egr-1 (ZENK) expression, an immediate early gene product used as marker of neural activation in birds, in the areas of interest. In contrast, in high experience animals, egr-1 expression in the POM, BST, and the periaqueductal gray (PAG) was not different than the level of expression in unmated controls. These results show that experience modulates the level of immediate early gene expression in the case of sexual behavior. Our results also indicate that immediate early gene expression in specific brain areas is not necessarily related to behavioral output but depends on the behavioral history of the subjects.

Cortisol controls the pubertal development of agonistic behavior in male golden hamsters via type II corticosteroid receptors.

In male golden hamsters, agonistic behavior undergoes a pubertal transition from play fighting to adult aggression. Previous studies have shown that this aspect of behavioral development is associated with pubertal increases in glucocorticoids and that daily social stress or injections of a synthetic glucocorticoid accelerate the transition. The goals of this study were to confirm the effects of cortisol on the development of agonistic behavior and to investigate the role of type II corticosteroid receptors in this process. First, animals treated with cortisol during early puberty [from postnatal days 31 (P-31) to P-36] showed an accelerated transition from play fighting to adult aggression. In a second experiment, the behavioral effects of cortisol were blocked by a co-treatment with a type II corticosteroid receptor antagonist. These findings are the first to show a facilitating role for type II corticosteroid receptors in the pubertal development of a social behavior. As such, these findings provide new insights into the neuroendocrine mechanisms controlling behavioral development during puberty.

Characterization of offensive responses during the maturation of play-fighting into aggression in male golden hamsters.

In hamsters, the maturation of aggression during puberty is associated with a gradual reduction of offensive responses. The purpose of this study was to analyze the changes during this decrease to provide an enhanced description of the behavior. During early puberty, play-fighting is characterized by long and continuous contact duration throughout the encounter and repetitive attacks within bouts of agonistic interaction. By mid-puberty, adult patterns of offensive behavior emerge. Contact time becomes shorter in duration and shifts to the beginning of the test, while attacks become less repetitive per bout. In late puberty, animals show an enhanced efficiency of behavior, as indicated by an increased percentage of attacks followed by bites. This study provides a better understanding of the development of aggression by characterizing the differences between juvenile play-fighting and adult aggression and the process of the maturation of aggression.

Differential responsiveness to fluoxetine during puberty.

In male golden hamsters (Mesocricetus auratus), attack frequency decreases during puberty. As serotonin inhibits offensive responses in adult hamsters, it is hypothesized that the serotonin system becomes upregulated in the hypothalamus during puberty. This hypothesis was tested through acute treatment with fluoxetine, a serotonin reuptake inhibitor, as well as through analysis of serotonin innervation in specific brain areas. In adults, fluoxetine treatment inhibited aggressive behavior. In juveniles, high doses of fluoxetine only reduced offensive responses (i.e., frequency and repetition of attacks), whereas low doses enhanced them. Juveniles also showed a dose-specific maturation of attack targets. In addition, the density of serotonin innervation of the hypothalamus was 20% higher in adult hamsters compared with juveniles. On the basis of these data, it is proposed that the developing serotonergic system shapes the development of offensive behaviors in male golden hamsters.

Stress facilitates consolidation of verbal memory for a film but does not affect retrieval.

The effect of psychosocial stress on distinct memory processes was investigated in 157 college students using a brief film, which enabled comparison of verbal and visual memory by using a single complex stimulus. Participants were stressed either following stimuli presentation (consolidation) or before testing 48 hr later (retrieval) and were compared with no-stress controls. Salivary cortisol was measured before and 20 min after stress. The consolidation group significantly outperformed controls on total and verbal film scores. Stress did not impair retrieval relative to controls. Exploratory analyses revealed a significant correlation between cortisol and verbal scores across all groups (r = .18). Results provide the first evidence of a facilitative effect of a stressor on verbal memory, but failed to replicate retrieval findings.

Distribution of orexin/hypocretin immunoreactivity in the brain of a male songbird, the house finch, Carpodacus mexicanus.

Previous research has shown orexin/hypocretin immunoreactive (orexin-ir) neurons in domesticated Galliformes. However, these findings may not be representative of other birds and these studies did not include a distribution of orexin-ir projections throughout the brain. The present study was carried out in a wild-caught passerine, the house finch, Carpodacus mexicanus, and includes a detailed description of orexin-ir neurons and their projections. Orexin A and B-ir neurons were located in a single population centered on the paraventricular nucleus of the hypothalamus extending into the lateral hypothalamic area, consistent with other studies in birds. Orexin A and B-ir fibers were similarly visible across the brain, with the highest density within the preoptic area, hypothalamus and thalamus. Orexin-ir projections extended from the paraventricular nucleus rostrally to the preoptic area, laterally towards the medial striatum, nidopallium, and dorsally along the lateral ventricle towards the mesopallium. Caudally, the highest densities of orexin-ir fibers were found along the third ventricle. The periaqueductal grey, substantia nigra pars compacta and the locus coeruleus also showed a high density of orexin-ir fibers. This study showed a detailed fiber distribution previously unreported in birds and showed that orexin-ir neurons were located in similar areas regardless of phylogeny or domestication in birds. The apparently conserved neural distribution of orexins suggests that these peptides play similar roles among birds. The widespread distribution of the projections in brain areas serving various roles indicates the potential involvement of these peptides in multiple behavioral and physiological functions.