S.M. Korte

Coping styles in animals: current status in behavior and stress-physiology

This paper summarizes the current views on coping styles as a useful concept in understanding individual adaptive capacity and vulnerability to stress-related disease. Studies in feral populations indicate the existence of a proactive and a reactive coping style. These coping styles seem to play a role in the population ecology of the species. Despite domestication, genetic selection and inbreeding, the same coping styles can, to some extent, also be observed in laboratory and farm animals. Coping styles are characterized by consistent behavioral and neuroendocrine characteristics, some of which seem to be causally linked to each other. Evidence is accumulating that the two coping styles might explain a differential vulnerability to stress mediated disease due to the differential adaptive value of the two coping styles and the accompanying neuroendocrine differentiation.

The Darwinian concept of stress: Benefits of allostasis and costs of allostatic load and the trade-offs in health and disease.

Why do we get the stress-related diseases we do? Why do some people have flare ups of autoimmune disease, whereas others suffer from melancholic depression during a stressful period in their life? In the present review possible explanations will be given by using different levels of analysis. First, we explain in evolutionary terms why different organisms adopt different behavioral strategies to cope with stress. It has become clear that natural selection maintains a balance of different traits preserving genes for high aggression (Hawks) and low aggression (Doves) within a population. The existence of these personality types (Hawks-Doves) is widespread in the animal kingdom, not only between males and females but also within the same gender across species. Second, proximate (causal) explanations are given for the different stress responses and how they work. Hawks and Doves differ in underlying physiology and these differences are associated with their respective behavioral strategies; for example, bold Hawks preferentially adopt the fight-flight response when establishing a new territory or defending an existing territory, while cautious Doves show the freeze-hide response to adapt to threats in their environment. Thus, adaptive processes that actively maintain stability through change (allostasis) depend on the personality type and the associated stress responses. Third, we describe how the expression of the various stress responses can result in specific benefits to the organism. Fourth, we discuss how the benefits of allostasis and the costs of adaptation (allostatic load) lead to different trade-offs in health and disease, thereby reinforcing a Darwinian concept of stress. Collectively, this provides some explanation of why individuals may differ in their vulnerability to different stress-related diseases and how this relates to the range of personality types, especially aggressive Hawks and non-aggressive Doves in a population. A conceptual framework is presented showing that Hawks, due to inefficient management of mediators of allostasis, are more likely to be violent, to develop impulse control disorders, hypertension, cardiac arrhythmias, sudden death, atypical depression, chronic fatigue states and inflammation. In contrast, Doves, due to the greater release of mediators of allostasis (surplus), are more susceptible to anxiety disorders, metabolic syndromes, melancholic depression, psychotic states and infection.

Corticosteroids in relation to fear, anxiety and psychopathology

Corticosteroids play extremely important roles in fear and anxiety. The mechanisms by which corticosteroids exert their effects on behavior are often indirect, because, although corticosteroids do not regulate behavior, they induce chemical changes in particular sets of neurons making certain behavioral outcomes more likely in certain contexts as a result of the strengthening or weakening of particular neural pathways. The timing of corticosteroid increase (before, during or after exposure to a stressor) determines whether and how behavior is affected. The present review shows that different aspects of fear and anxiety are affected differentially by the occupation of the mineralocorticoid receptor (MR) or glucocorticoid receptor (GR) at different phases of the stress response. Corticosteroids, at low circulating levels, exert a permissive action via brain MRs on the mediation of acute freezing behavior and acute fear-related plus-maze behavior. Corticosteroids, at high circulating levels, enhance acquisition, conditioning and consolidation of an inescapable stressful experience via GR-mechanisms. Brain GR-occupation also promotes processes underlying fear potentiation. Fear potentiation can be seen as an adjustment in anticipation of changing demands. However, such feed-forward regulation may be particularly vulnerable to dysfunction. MR and/or GR mechanisms are involved in fear extinction. Brain MRs may be involved in the extinction of passive avoidance, and GRs may be involved in mediating the extinction of active avoidance. In the developing brain, corticosteroids play a facilitatory role in the ontogeny of freezing behavior, probably via GRs in the dorsal hippocampus, and their influence on the development of the septo-hippocampal cholinergic system. Corticosteroids can exert maladaptive rather than adaptive effects when their actions via MRs and GRs are chronically unbalanced due to chronic stress. Both mental health of humans and animal welfare is likely to be seriously threatened after psychosocial stress, prolonged stress, prenatal stress or postnatal stress, especially when maternal care or social support is absent, because these can chronically dysregulate the central MR/GR balance. In such circumstances the normally adaptive corticosteroid responses can become maladaptive.

Housing familiar male wildtype rats together reduces the long-term adverse behavioural and physiological effects of social defeat.

Social stress in rats is known to induce long-lasting, adverse changes in behaviour and physiology, which seem to resemble certain human psychopathologies, such as depression and anxiety. The present experiment was designed to assess the influence of individual or group housing on the vulnerability of male Wildtype rats to long-term effects of inescapable social defeat. Group-housed rats were individually exposed to an aggressive, unfamiliar male conspecific, resulting in a social defeat. Defeated rats were then either individually housed or returned to their group. The changes in their behaviour and physiology were then studied for 3 weeks. Results showed that individually housed rats developed long-lasting, adverse behavioural and physiological changes after social defeat. Their body growth was significantly retarded (p < .05) between 7 and 14 days after defeat. When individually and group-housed rats were exposed to a mild stressor (sudden silence) 2 days after defeat, both groups became highly immobile. However, when exposure was repeated at day 21, individually housed rats were still highly immobile compared to group-housed rats which regained their normal mobility after only 7 days. In an open field test, also regularly repeated, individually housed rats took significantly longer to leave their home base and were also significantly less mobile than group-housed rats over the entire 3-week test period as well as at specific timepoints. When the rats were placed in an elevated plus-maze 14 days after defeat, those that were individually housed were significantly more anxious than those that were group-housed. When tested at 21 days after defeat in a combined dexamethasone (DEX)/corticotrophin-releasing factor (CRF) test, results showed that the hypothalamic-pituitary-adrenocortical (HPA) activity in individually housed rats was higher. This was evidenced in the latter animals by the fact that DEX was significantly less able to suppress the secretion of ACTH and corticosterone, and by a significantly higher release of ACTH after administration of CRF. Although the weights of the spleen and testes of the two groups did not differ, the adrenals of individually housed rats were larger and the thymus and seminal vesicles were smaller. We conclude that when rats are isolated after defeat, they show long-lasting, adverse behavioural and physiological changes that resemble symptoms of stress-related disorders. In contrast, when familiar rats are housed together these effects of a social defeat are greatly reduced. These findings show that housing conditions importantly influence the probability of long-term adverse behavioural and physiological effects of social defeat in male Wildtype rats.

Effects of environmental enrichment on behavioral responses to novelty, learning, and memory, and the circadian rhythm in cortisol in growing pigs

Previously we showed that pigs reared in an enriched environment had higher baseline salivary cortisol concentrations during the light period than pigs reared under barren conditions. In the present experiment, it was investigated whether these higher baseline salivary cortisol concentrations were a real difference in cortisol concentration or merely represented a phase difference in circadian rhythm. The effects of different cortisol concentrations on the behavioral responses to novelty and learning and long-term memory in a maze test were also studied in enriched and barren housed pigs. At 9 weeks of age enriched and barren housed pigs did not differ in baseline salivary cortisol concentrations nor in circadian rhythm, but at 22 weeks of age barren housed pigs had a blunted circadian rhythm in salivary cortisol as compared to enriched housed pigs. The differences in baseline salivary cortisol concentrations between enriched- and barren-housed pigs are age-dependent, and become visible after 15 weeks of age. Enriched- and barren-housed piglets did not differ in time spent on exploration in the novel environment test. Barren-housed pigs had an impaired long-term memory in the maze test compared to enriched-housed pigs; however, no differences in learning abilities between enriched- and barren-housed pigs were found. Because blunted circadian cortisol rhythms are often recorded during states of chronic stress in pigs and rats or during depression in humans, it is suggested that the blunted circadian rhythm in cortisol in barren-housed pigs similarily may reflect decreased welfare.

ANXIOLYTIC-LIKE EFFECTS OF SELECTIVE MINERALOCORTICOID AND GLUCOCORTICOID ANTAGONISTS ON FEAR-ENHANCED BEHAVIOR IN THE ELEVATED PLUS-MAZE

The effects of intracerebroventricular (ICV) administration of the mineralocorticoid receptor (MR) antagonist, RU28318, and the glucocorticoid receptor (GR) antagonist, RU38486, were studied on behavior of rats exposed to a compartment previously associated with a stressor, and placed subsequently in an elevated plus-maze test. Fear-motivated immobility behavior was attenuated by the MR antagonist in a dose of 50 or 100 ng ICV, whereas the GR antagonist alone or simultaneous administration of both antagonists had no significant effect. In the elevated plus-maze, immediately after the exposure to the conditioned stressor, both the GR antagonist (50 ng) and MR antagonist (50 ng) increased the percentage of time the rats spent on open arms, and increased the amount of entries into these open arms. These data are interpretated in terms of the involvement of the GR and MR in fear and anxiety.

Enhanced 5-HT1A receptor expression in forebrain regions of aggressive house mice.

The brain 5-HT1A receptor system in male wild house mice selected for high and low offensive aggression was investigated by autoradiographic analysis of in situ hybridization and radioligand binding. In high-aggressive mice, characterized by a short attack latency, the rise in plasma corticosterone concentration during the early dark phase was reduced. At that time the level of 5-HT1A mRNA in the dorsal hippocampus (dentate gyrus and CA1) was twice the amount measured in low-aggressive mice that had long attack latency and high plasma corticosterone level. Increased postsynaptic 5-HT1A receptor radioligand binding was found in dentate gyrus, CA1, lateral septum, and frontal cortex. No difference in ligand binding was found for the 5-HT1A autoreceptor on cell bodies in the dorsal raphe nucleus. In conclusion, genetic selection for high offensive aggression co-selects for reduced (circadian peak) level in plasma corticosterone and increased postsynaptic 5-HT1A receptor number in limbic and cortical regions.

Effects of strawbedding on physiological responses to stressors and behavior in growing pigs

To study the effects of environmental enrichment on physiological responses to stressors and behavior in growing pigs, pigs were housed in either a poor environment (standard farrowing pens followed by standard rearing and fattening pens) or in an enriched environment (larger farrowing pens followed by larger rearing and fattening pens, provision of straw). Body temperature, heart rate and salivary cortisol were measured during baseline conditions and in response to relocation, isolation and restraint. Pigs housed in the poor environment performed more manipulative social behavior directed to penmates than pigs housed in the enriched environment. Physiological responses to the stressors were the same for enriched- and poor-housed pigs. Surprisingly, enriched-housed pigs had significantly higher baseline salivary cortisol concentrations, especially at 14 and 17 weeks of age. Moreover, enriched housed pigs had a lower baseline body temperature at 17 weeks of age. Thus, provision of straw has an effect on behavior, baseline HPA-axis activity and baseline body temperature in growing pigs.

Antisense to the glucocorticoid receptor in hippocampal dentate gyrus reduces immobility in forced swim test

Immobility time of rats in the forced swim test was reduced after bilateral infusion of an 18-mer antisense phosphorothioate oligodeoxynucleotide targeted to the glucocorticoid receptor mRNA into the dentate gyrus of the hippocampus. Vehicle-, sense- and scrambled sequence-treated animals spent significantly more time immobile than antisense-treated animals during the initial test. Immunolabeling of the glucocorticoid receptor in brain sections demonstrated a reduced expression of glucocorticoid receptor proteins in antisense-treated dentate gyrus compared to the contralateral sense-treated dentate gyrus or contralateral scrambled sequence-treated dentate gyrus. During the initial test the time spent on immobility was also reduced when rats were treated with the glucocorticoid receptor antagonist RU38486 (17 beta-hydroxy-11 beta-(4-dimethylamino-phenyl)17 alpha-(1-propnyl)estra-4,9-diene-3-one)) 6 h (but not 1 h) earlier. These results demonstrate the participation of glucocorticoid receptors in the expression of immobility in a forced swim test during the initial test.

Behavioral stress response of genetically selected aggressive and nonaggressive wild house mice in the shock-probe/defensive burying test

Genetically selected aggressive and nonaggressive male wild house mice were tested in the shock-probe/defensive burying test: Five distinct behaviors (burying, immobility, rearing, grooming, and exploration) were recorded in two environmental situations: fresh and home cage sawdust. Nonaggressive animals, characterized by a Long Attack Latency (LAL), showed more immobility in both test situations than animals having Short Attack Latencies (SAL), whereas SAL males displayed more defensive burying than LAL ones when tested with fresh sawdust. Testing with home cage sawdust, however, resulted in the same duration of defensive burying in SAL and LAL. These results support earlier findings about the existence of two heritable, fundamentally different strategies to cope with aversive situations. Aggressive (SAL) animal react actively to environmental challenges, whereas nonaggressive animals react actively or passively, depending on the characteristics of the stressful environment. These mouse lines, selected for attack latency, i.e., aggression, may, therefore, be important tools to unravel the genetic architecture underlying the physiological and neuronal mechanisms of behavioral strategies towards stressful events.