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J M Koolhaas

Publications and source records attributed to J M Koolhaas.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of mild stress on the immune response against pseudorabies virus in mice.

Stress is a recognised problem in intensive pig husbandry, which might lead to changes in immune reactivity. To study the effect of stress on the development of an anti-viral immune response, we used a murine model in which mice were immunized with an attenuated strain of pseudorabies virus (PRV). The effect of two stress treatments, both relevant to intensive pig husbandry, on the development of the specific immune response against PRV was investigated. The stress treatments consisted of restraint, social isolation, and transport and they differed in predictability. The specific immune response against PRV, which developed in the draining lymph nodes, was measured by a lymphocyte proliferation assay and cytokine production assays. Our results showed that the unpredictable stress treatment had no effect on the development of the immune response against PRV in mice, whereas the predictable stress treatment actually hastened the immune response.

Animals↗
PubMed1999

Individual behavioral characteristics of wild-type rats predict susceptibility to experimental autoimmune encephalomyelitis.

Neuroendocrine-immune interactions are thought to be important in determining susceptibility to autoimmune disease. Animal studies have revealed that differences in susceptibility to experimental autoimmune encephalomyelitis (EAE) are related to reactivity in the hypothalamo-pituitary-adrenal axis. It is known that there is a close relation between neuroendocrine parameters and behavioral characteristics, suggesting that behavior and disease susceptibility may be associated. In the present study we investigated whether behavioral characteristics of wild-type rats are related to susceptibility to disease. We show here that the latency of the animal to attack an intruder correlates significantly with the EAE disease score: animals that do not attack the intruder during the test period are more resistant to the disease than animals with short attack latency times. These data, obtained in an unselected strain of wild-type rats, demonstrate that behavioral response patterns of individual animals can in part predict susceptibility to autoimmune disease.

Aggression↗
PubMed1999

Different sympathovagal modulation of heart rate during social and nonsocial stress episodes in wild-type rats.

The acute consequences of a social aversive stimulus (defeat) on the autonomic control upon the electrical activity of the heart were measured and compared to those observed in three nonsocial stress paradigms, namely restraint, shock-probe test, and swimming. Electrocardiograms were recorded from rats via radiotelemetry, and the autonomic neural control of the heart was evaluated via measures of heart rate and heart rate variability, such as the average R-R interval (RR), the standard deviation of RR (SD), the coefficient of variance (SD/RR), and the root-mean-square of successive R-R interval differences (r-MSSD). Although all stressors induced significant reductions of average R-R interval, the effect of defeat was significantly larger (p < 0.05). The social stimulus also determined a significant decrease in the variability indexes (p < 0.01 for all), whereas in the other stress conditions they were either unchanged or increased (SD/RR during restraint, p < 0.05; SD and SD/RR during swimming, p < 0.05 and p < 0.01). Cardiac arrhythmias (mostly ventricular premature beats, VPBs) were far more frequent during defeat than during the other challenging situations (p < 0.01), with an average of 33.5 +/- 6.5 VPBs per 15-min test recording. These data suggest that during defeat autonomic control was shifted toward a sympathetic dominance, whereas in rats exposed to nonsocial stressors, although significant heart rate accelerations were also found, sympathovagal balance was substantially maintained. These differences in autonomic stress responsivity explain the different susceptibility to ventricular arrhythmias and indicate that a social challenge can be far more detrimental for cardiac electrical stability than other nonsocial aversive stimuli.

Animals↗
PubMed1999

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.

Adaptation, Psychological↗
PubMed1999

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.

Adrenal Cortex↗
PubMed1999

Long-lasting consequences of a social conflict in rats: behavior during the interaction predicts subsequent changes in daily rhythms of heart rate, temperature, and activity.

This study shows that the long-term consequences of a social conflict in rats do not depend on the physical intensity of the fight in terms of aggression received but, especially, on how the subjects deal with it. Experimental rats were introduced into the cage of an aggressive conspecific for 1 hr, and the effects on daily rhythms of heart rate, body temperature, and activity thereafter were measured by means of telemetry. In some rats, the confrontation caused a strong decrease in the daily rhythm amplitude that lasted up to 3 weeks, whereas other subjects showed only minor changes. The changes in rhythm amplitude did not correlate with the number of attacks received from the territory owner. Contrary to this, the changes showed a clear negative correlation with the aggression of the experimental rats themselves. Subjects fighting back and counterattacking the cage owner subsequently had a smaller reduction in rhythm amplitude.

Aggression↗
PubMed1999

Long-lasting deficient dexamethasone suppression of hypothalamic-pituitary-adrenocortical activation following peripheral CRF challenge in socially defeated rats.

The present study focuses on the long-term changes in the regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis following two short-lasting episodes of intensive stress in the rat stress model of social defeat and the possible similarities with HPA functioning in human affective disorders. Male Wistar rats experienced social defeats on 2 consecutive days by an aggressive male conspecific. The long-term effect of these defeats on resting and ovine corticotropin-releasing factor (oCRF; intravenous (i.v.) 0. 5 microg/kg) induced levels of plasma ACTH and corticosterone (CORT) were measured 1 and 3 weeks later. In a second experiment the glucocorticoid feedback regulation of HPA function was tested in a combined dexamethasone (DEX)/CRF test (DEX; 25 microg/kg s.c., 90 min before oCRF injection, 0.5 microg/kg). The oCRF challenges were performed between 11.00 and 13.00 h (about three hours after start of the light phase). One week after defeat the ACTH response to CRF was significantly enhanced in defeated rats as compared to controls. Three weeks after defeat the ACTH response was back to control levels. The increased ACTH response 1 week after the stressor was not reflected in higher CORT levels. Neither were baseline ACTH and CORT levels affected by the prior stress exposure. DEX pretreatment inhibited pituitary adrenocortical activity, reflected both in reduced baseline and response values of ACTH and CORT. The ACTH response to CRF following DEX administration was significantly higher in defeated rats as compared to controls both at one and three weeks after defeat. A reduced DEX suppression of baseline secretion of ACTH appeared 3 weeks after defeat. The same tendency was apparent in response and baseline values of CORT. The differences in CORT between socially stressed and control treated rats, however, did not reach significance. The possible role of changes in glucocorticoid-(GR) and mineralocorticoid receptor (MR) binding in the altered regulation of HPA activity following defeat were studied in brain and pituitary of male Wistar rats 1 and 3 weeks after defeat. One week after defeat GR-binding decreased in hippocampus and hypothalamus. No changes were observed in GR-binding in the pituitary nor in MR-binding in any of the regions analysed. Three weeks after defeat GR-binding recovered in hippocampus and hypothalamus but at this time MR-binding in hippocampal tissue was seriously decreased. In a fourth experiment vasopressin (AVP) and CRF stores in the external zone of the median eminence (ZEME) were measured by quantitative immunocytochemistry one and three weeks after defeat and compared with controls. Social defeat failed to induce a change in the immunocytochemical stores of AVP or CRF. The present findings show that in rats short-lasting stressors like defeat induce long-lasting, temporal dynamic changes in the regulation of the HPA axis. Since these changes in time are reflected in GRs and MRs in different brain areas an altered corticosteroid receptor binding might play an important role in the affected HPA activity following defeat.

Adrenal Cortex↗
PubMed1999

The influence of postnatal handling on adult neuroendocrine and behavioural stress reactivity.

Environmental stimuli during early stages of life can influence the development of an organism and may result in permanent changes in adult behaviour and physiology. In the present study we investigated the influence of early postnatal handling on adult neuroendocrine and behavioural stress reactivity in Wistar rats. Pups were subjected to handling from postnatal day 1-21. The young were taken from the nest every day for 15 min and each of the pups was handled separately. Control nests were left undisturbed. When the animals had reached an adult age of 3-4 months they were individually housed and subjected to a series of tests to measure their stress reactivity. In the first experiment we established adult behavioural coping with stressors and anxiety in the following series of tests: open field test, shock prod defensive burying test, elevated plus maze and conditioned fear test. Collectively, the data clearly indicate that handled animals are characterized by a lower stress-induced anxiety. Yet, handled and control animals do not differ in their general way of coping with stressors. Although the lower anxiety in handled animals is often reflected in a higher activity, they are not more active per se. In a second experiment, animals were provided with a permanent jugular vein canula for repeated blood sampling to determine stress hormones: noradrenaline, adrenaline, prolactin and corticosterone. Animals were subjected to a novelty test and a conditioned fear test. The neuroendocrine response profile is consistent with the conclusion that handled animals are less anxious than controls but are not different in their general strategy of coping with stressors. The handled animals showed an attenuated adrenaline, prolactin and corticosterone response. Yet, in neither of the two tests there was a difference in noradrenaline response, a typical marker for an active coping strategy. Interestingly, the differences in neuroendocrine reactivity already appeared in response to a mild novelty challenge when there were no clear behavioural differences yet. The neuroendocrine measures are in line with the behavioural data but more sensitively reflect the differences between handled and control animals.

Adaptation, Psychological↗
PubMed1999

Selective antiaggressive effects of alnespirone in resident-intruder test are mediated via 5-hydroxytryptamine1A receptors: A comparative pharmacological study with 8-hydroxy-2-dipropylaminotetralin, ipsapirone, buspirone, eltoprazine, and WAY-100635.

The present study characterized the effects of the novel, selective, and potent 5-hydroxytryptamine1A (serotonin) (5-HT1A) receptor agonist, alnespirone [S-20499, (S)-N-4-[5-methoxychroman-3-yl)propylamino)butyl- 8-azaspiro-(4,5)-diacetamide, hydrochloride] on offensive and defensive resident-intruder aggression in wild-type rats and compared its actions with those of the prototypical full 5-HT1A agonist 8-hydroxy-2- dipropylaminotetralin (8-OH-DPAT), the partial 5-HT1A agonists ipsapirone and buspirone, and the mixed 5-HT1A/1B agonist eltoprazine. All five agonists exerted effective dose-dependent decreases of offensive aggressive behavior in resident rats; 8-OH-DPAT was the most potent (ID50 = 0.074 mg/kg), followed by eltoprazine (0.24), buspirone (0.72), ipsapirone (1.08), and alnespirone (1.24). However, in terms of selectivity of the antiaggressive effects as determined by the absence of decrements in social interest and general motor activity, alnespirone appeared to be superior. In the defensive aggression test, neither alnespirone nor any of the other four agonists changed defensive behaviors in the intruder rats. The involvement of 5-HT1A receptors in the antiaggressive actions of these drugs was confirmed by showing that the selective 5-HT1A receptor antagonist WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2- pyridinyl)cyclohexanecarboxamide trihydrochloride), which was inactive alone, fully prevented the antiaggressive effects of alnespirone, 8-OH-DPAT, and buspirone and partly reversed those of ipsapirone and eltoprazine. The data clearly indicate that alnespirone effectively suppresses offensive aggression with an advantageous profile of action compared with other full or partial 5-HT1A agonists. These selective antiaggressive actions of alnespirone are mediated by stimulating 5-HT1A receptors, presumably the somatodendritic autoreceptors at the raphe nuclei. Furthermore, the data provide evidence for a major involvement of these 5-HT1A receptors in the modulation of aggressive behavior by 8-OH-DPAT, ipsapirone, buspirone, and eltoprazine.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1999

Play is indispensable for an adequate development of coping with social challenges in the rat.

In this study, young rats were deprived of early social interactions during weeks 4 and 5 of life. Different behavioral tests were conducted in adulthood to study the behavioral responses of rats lacking early social experiences. Juvenile deprivation resulted in decreased social activity and an altered sexual pattern, but did not affect locomotor activity or the performance in the elevated plus maze. Furthermore, behavioral and neuroendocrine responses of juvenile isolated rats were dramatically altered when they were confronted with territorial aggression. Juvenile deprived rats did not readily display a submissive posture in response to the resident and showed no immobility behavior after being returned to the resident's territory, while their plasma corticosterone and adrenaline concentrations were significantly increased compared to nonisolated controls. In contrast, behavioral responses in the shock prod test were not affected by previous isolation. The results suggest that early social experiences are vital for interactions with conspecifics later in life, i.e., aggression, sexual, and social interactions.

Adaptation, Psychological↗
PubMed1998

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.

Adrenal Glands↗
PubMed1998

Coping with stress in rats and mice: differential peptidergic modulation of the amygdala-lateral septum complex.

This chapter focuses on the parvicellular vasopressin (VP) system originating from the medial nucleus of the amygdala (MeA) and bed nucleus of the stria terminalis (BNST). The vasopressinergic fibers of these nuclei innervate a number of limbic brain areas including the septum-hippocampal complex. Interestingly, this VP system is sexually dimorphic and the VP synthesis in this system depends on circulating gonadal steroids. Studies in rats and mice show that the variation in the lateral septal VP network within the male gender is as large as the variation between the sexes as reported in the literature. Non-aggressive males are characterized by a far more extensive VP network and a higher VP content in the lateral septal area than aggressive males. A review of the literature on the function of lateral septal VP in the organization of behavior reveals not only a modulatory role of behavior in a social context, but also of fear- and anxiety-related behaviors. It is argued that these seemingly diverse functions might be explained by the concept of coping style. Extensive behavioral and physiological analyses in a variety of animal species show that males may be characterized by the way in which they cope with environmental challenges in general. Aggressive males tend to cope actively with their environment whereas non-aggressive males seem to accept the situation as it is more easily. In several tests, we determined the effects of chronic infusion of the V1 receptor antagonist locally into the lateral septal area in male rats. The main conclusion from these experiments is that LS VP does not modulate coping style in general. However, the experiments confirm the idea that LS VP has a certain degree of functional specificity in social behavior and social learning tasks. Together with the observation that the size and distribution of the vasopressinergic system may be highly variable between individual males in relation to their coping style, this suggests that the lateral septal vasopressinergic system is involved in the differential capacity of individuals to cope behaviorally with challenges of a social nature.

Adaptation, Psychological↗
PubMed1998

Behavioral and physiological consequences of repeated daily intracerebroventricular injection of corticotropin-releasing factor in the rat.

The present study was conducted to investigate the long-term consequences of repeated daily bolus injections of corticotropin-releasing factor (CRF) intracerebroventricularly (ICV) on ongoing locomotor activity and physiology in the home cage of individually housed rats. For this purpose ovine CRF (1 microgram/3 microliters) was injected once daily during the early resting phase into the lateral ventricle for a period of 10 days. Changes in daily rhythms in heart rate, body temperature and motor activity were recorded telemetrically before and during the treatment period. Daily central CRF injection delayed the body weight gain, increased adrenal weight, and decreased the weight of the thymus at the end of the experiment. The acute behavioral and physiological responses to CRF did not habituate with repetition of treatment. CRF treatment also failed to affect the long-term regulation of baseline heart rate, body temperature and motor activity during the light phase, as measured during the hour preceding the daily CRF injection. Mean heart rate during the dark phase was, however, significantly decreased in CRF-treated rats during the whole experimental 10-day period, without any sign of habituation. The failure of episodic CRF to affect long-term regulation of baseline body temperature during the light as well as the dark phase was noteworthy because an increased daytime body temperature lasting for several days is a characteristic marker of various behavioral stressors. Since a previous study showed that the temperature response during chronic CRF infusion was similar to the long-term effects of behavioral stress it is hypothesized that chronic but not episodic increases in central CRF levels are related to the induction and persistence of part of the stress-related behavioral and physiological disorders.

Animals↗
PubMed1998

Differential effects of CRH infusion into the central nucleus of the amygdala in the Roman high-avoidance and low-avoidance rats.

Roman-high (RHA/Verh) and low (RLA/Verh) avoidance rats are selected and bred for rapid learning versus non-acquisition of two-way, active avoidance behavior in a shuttle box. RHA/Verh rats generally show a more active coping style than do their RLA/Verh counterparts when exposed to various environmental challenges. The central nucleus of the amygdala (CeA) is known to be involved in the regulation of autonomic, neuroendocrine and behavioural responses to stress and stress-free conditions, and it is considered in relation to coping strategies. Corticotropin-releasing hormone (CRH) seems to be a key factor in the control of the CeA output. Neuroanatomical studies have revealed that the majority of CRH fibers from the CeA have direct connections with autonomic regulatory nuclei in the brainstem, e.g. lateral parabrachial nucleus (lPB), ventrolateral periaquaductal gray (vlPAG). The modulating effects of CRH (30 ng) on CeA activity were studied by infusion of CRH into the CeA in freely moving male RHA/Verh and RLA/Verh rats under stress-free conditions. Heart-rate and behavioural activities were repeatedly measured before, during and after local administration of CRH or vehicle, after which early gene product FOS immunocytochemistry and CRH-mRNA in situ hybridisation were carried out in selected brain areas. CRH infusion into the CeA caused a long lasting increase in heart-rate and behavioural activation in the RHA/Verh rats, leaving the RLA/Verh rats unaffected. As a result of CRH infusion, the number of FOS positive cells in the CeA and lPB of RLA/Verh rats was increased whereas an opposite response was found in the RHA/Verh rats. However, CRH into the CeA of the Roman rat lines induced no pronounced effects on FOS staining in the vlPAG and CRH mRNA levels in the CeA. These results indicate that the CRH system of the CeA, connected with the output brainstem areas, is differentially involved in cardiovascular and behavioural responses.

Adaptation, Psychological↗
PubMed1998

Vulnerability to arrhythmias during social stress in rats with different sympathovagal balance.

An increased activity of the sympathetic nervous system is an important factor in the genesis of ventricular arrhythmias. Changes in average R-R interval, R-R interval variability (indirect measure of sympathovagal balance), occurrence of arrhythmias, and plasma norepinephrine concentrations were measured during a social stress episode (defeat) in two strains of rats, Wistar and wild type, which were supposed to differ in their autonomic stress responsiveness. Electrocardiograms were telemetrically recorded, and blood samples were withdrawn through jugular vein catheters from healthy, freely moving animals. R-R interval variability was estimated by the following time-domain parameters: the standard deviation of the mean R-R interval, the coefficient of variance, and the root mean square of successive differences in R-R interval. Average R-R interval and R-R interval variability measures, as well as plasma norepinephrine concentrations, indicated a higher sympathetic tone, a larger sympathetic responsiveness, and a lower parasympathetic antagonism after sympathetic activation in wild-type animals, which also showed a much higher incidence of arrhythmias (ventricular premature beats), compared with Wistar rats. These two strains might represent a valuable experimental model for studying the mechanisms (cellular/electrophysiological) responsible for the susceptibility to arrhythmias in healthy individuals exposed to stressful situations.

Analysis of Variance↗
PubMed1997

Lateral septal vasopressin in rats: role in social and object recognition?

The capacity of male rats to remember familiar conspecifics is called social recognition. It is a form of short-term memory modulated by lateral septal (LS) vasopressin (VP). The specificity of this phenomenon was studied by examining whether recognition of previously investigated objects is also under control of lateral septal VP. For social recognition male Wistar rats were confronted with juveniles for 5 min. Re-exposure to the same juvenile took place after 30 or 120 min, or with a different juvenile after 30 min. This procedure was duplicated for object recognition using a plastic food cup or a 50 ml Erlenmeyer flask. After these initial tests osmotic minipumps and brain cannulae were implanted, infusing VP receptor antagonist into the LS (dPTyr(Et)AVP, 1 ng/0.5 microl/h, bilateral). Animals were re-tested for social and object recognition using 30 min re-test interval (same juvenile or object). We reproduced previous reports concerning social recognition; animals recognized juveniles after 30 min, not after 120 min and VP antagonist treatment blocked recognition. Testing for object recognition revealed a reduction in investigation time at the 30 min interval (same and different object), but not after 120 min. VP antagonist treatment was unable to block object recognition. The data suggest that, in contrast to social recognition, object recognition reflects a form of habituation, which is not under the control of lateral septal VP.

Animals↗
PubMed1997

Differential lateral septal vasopressin in wild-type rats: correlation with aggression.

The vasopressin (VP)-containing projections from the cells of the bed nucleus of the stria terminalis to the lateral septum (LS) are sexually dimorphic and dependent on gonadal steroids. Recently, the difference in VP distribution found among both sexes was also demonstrated in male mice genetically selected for different levels of intermale aggression. In the present study we examined whether this differential VP distribution in males also exists in an outbred strain of wild-type rats. After the animals were tested for their level of aggression, the VP content and the fiber density of the LS were measured using radioimmunoassay and immunocytochemistry, respectively. In addition, basal levels of plasma testosterone (T) were measured. Both biochemical data and immunocytochemical data revealed a negative correlation between VP and intermale aggression. Aggressive rats exhibited low levels of VP whereas intermediate and nonaggressive animals showed higher levels. Differences in adult levels of T were not found. The results are in accordance with the observations previously found in male mice, reconfirming the correlation between lateral septal VP and aggression.

Aggression↗