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Biomedical subjects

B Bohus

Publications and source records attributed to B Bohus.

At least 91 records · Page 5Linked to original sources

Heritable variation for aggression as a reflection of individual coping strategies.

Evidence is presented in rodents, that individual differences in aggression reflect heritable, fundamentally different, but equally valuable alternative strategies to cope with environmental demands. Generally, aggressive individuals show an active response to aversive situations. In a social setting, they react with flight or escape when defeated; in non-social situations, they react with active avoidance of controllable shocks and with sustained activity during an uncontrollable task. In contrast, non-aggressive individuals generally adopt a passive strategy. In social and non-social aversive situations, they react with immobility and withdrawal. A main aspect of these two alternative strategies is that individuals with an active strategy easily develop routines (intrinsically determined behaviour), and consequently do not react (properly) to 'minor' changes in their environment, whereas in passively reacting animals it is just the other way around (extrinsically determined behaviour). It has become clear that active and passive behavioural strategies represent two different, but equivalent, coping styles. The coping style of the aggressive males is aimed at the removal of themselves from the source of stress or at removal of the stress source itself (i.e. active manipulation). Non-aggressive individuals seem to aim at the reduction of the emotional impact of the stress (i.e. passive confrontation). The success of both coping styles depends upon the variability or stability of the environment. The fact that aggressive males develop routines may contribute to a fast execution of their anticipatory responses, which is necessary for an effective manipulation of events. However, this is only of advantage in predictable (stable) situations, but is maladaptive (e.g. expressed by the development of stress pathologies) when the animal is confronted with the unexpected (variable situations). The flexible behaviour of non-aggressive individuals, depending strongly upon external stimuli, will be of advantage under changing conditions. Studies on wild house mice living under natural conditions show how active and passive coping functions in nature, and how the two types have been brought about by natural selection.

Adaptation, Psychological↗

Involvement of hypothalamic serotonin in activation of the sympathoadrenomedullary system and hypothalamo-pituitary-adrenocortical axis in male Wistar rats.

Infusion of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (2.5-20 micrograms in 1 microliter during 15 min), into the paraventricular nucleus of the hypothalamus (PVN) in the rat dose dependently increased plasma adrenaline and corticosterone concentrations, without affecting plasma noradrenaline concentrations. The highest dose also increased plasma glucose levels significantly. The results suggest that both the sympathoadrenomedullary system and the hypothalamo-pituitary-adrenocortical axis are activated after stimulation of 5-HT1A receptors in the PVN.

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

Behavioural differences between artificially selected aggressive and non-aggressive mice: response to apomorphine.

The present study reports a first attempt to unravel the neurochemical background that underlies the difference in behavioural profiles between aggressive and non-aggressive male mice. For this purpose two bidirectionally selected lines for attack latency (SAL and LAL) were used. In pursuit of Cools'9 approach, the susceptibility of individuals of both selection lines to the dopamine agonist apomorphine was measured. The apomorphine was injected subcutaneously at dose levels of 2.5 and 5.0 mg/kg. Apomorphine is considered to stimulate the dopamine receptors in the telencephalon and induces stereotyped behaviour. The responsivity to apomorphine can be rated as a total stereotypy-score. SAL (aggressive) mice showed a significantly greater enhancement of stereotyped behaviour in response to apomorphine than LAL (non-aggressive) mice. In addition, it was demonstrated that this difference is of a quantitative rather than qualitative character. Pharmacokinetic variation between the two lines could be ruled out as cause of the difference. Hence, it was concluded that SAL mice are more sensitive to apomorphine than LAL males, which provides evidence for a difference in the dopaminergic system between the two selection lines. It was suggested that this difference underlies the difference in flexibility in behaviour between aggressive and non-aggressive male mice.

Aggression↗

Attenuated cardiovascular, neuroendocrine, and behavioral responses after a single footshock in central amygdaloid lesioned male rats.

The effect of bilateral electrolytical CEA lesioning on behavioral, cardiovascular and neuroendocrine changes has been studied in male Wistar rats before, during and shortly after a brief aversive stimulus of an unavoidable footshock. Blood samples were withdrawn via a permanent heart catheter. Lesioning of the CEA abolished completely the immobility response normally seen after a footshock. Lesions failed to affect the early tachycardiac response compared to sham-lesioned controls, but the poststress recovery was attenuated, probably due to diminished vagal activation. Furthermore, the magnitude of the responses of all measured hormones (epinephrine, norepinephrine, corticosterone and prolactin) appeared to be attenuated in the lesioned rats. These results suggest that the CEA plays an important and general role in the behavioral, autonomic and hormonal output during a brief unavoidable, unconditioned footshock. This is in contrast with the selective role of the CEA in vagal (parasympathetic) and on inhibitory (immobility) behavioral responses following conditioning.

Amygdala↗

Central amygdala lesions affect behavioral and autonomic balance during stress in rats.

The effects of a bilateral electrolytical lesion of the CEA on the behavioral and sympathetically induced cardiac response in the shock-probe/defensive-burying test have been analyzed in male Wistar rats. Lesions in the CEA failed to affect defensive burying and accompanying tachycardiac response as compared to sham-lesioned controls during the presentation of the electrified shock probe (unconditioned test). However, CEA lesioning attenuated the bradycardiac response and the immobility behavior during the late part of the test. Retention of this behavior one day after the exposure to the probe (conditioned test) was attenuated by the lesion. However, when the lesion was placed after the unconditioned test situation, retention of the burying was not affected, but the animals failed to show immobility behavior. These results, in agreement with former studies, suggest that the CEA is involved particularly in the organization and/or expression of the passive component of the behavior and the parasympathetic outflow during stress. The active component, i.e., burying behavior, and the accompanying tachycardiac response remains unaffected unless the acquisition of the stress response took place with damaged CEA.

Amygdala↗

Effects of neonatal administration of vasopressin on cardiac and behavioral responses to emotional stress in adult male rats.

Arginine-8-vasopressin (AVP) was administered subcutaneously on postnatal days 3-7 in a high (10 micrograms/100 g b.wt.) or a low dose (1 microgram/100 g b.wt.) to male Wistar rats. Control pups were untreated or saline injected. Behavioral observations in a complex maze after maturation indicated that neonatal administration of AVP increases exploratory behavior in this novel environment in a dose-dependent way. Cardiac monitoring during the conditioned emotional stress of fear of inescapable electric footshock showed that only the high dose of AVP attenuates the bradycardiac stress response. The analysis of cardiac responses also suggested an adult hyposensitivity to AVP in rats treated neonatally with AVP. In addition, the low dose of neonatal AVP was impairing the retention of a passive avoidance behavior. The data indicate that the neonatal administration of AVP exerts long-term effects upon the behavioral adaptation to novelty and memory processes related to emotional stress. That neonatal AVP is less effective in influencing adult vagally mediated cardiac stress responses suggests differences in the developmental sensitivity ("critical periods") of the central vasopressinergic systems involved in the regulation of behavior and autonomic functioning.

Animals↗

Reduced preabsorptive insulin response in aged rats: differential effects of amphetamine and arginine-vasopressin.

The experiments presented here have been designed to investigated whether the age-related attenuation of the vagal reactivity to emotional stressors and its modulation by amphetamine (Amph) or arginine-vasopressin (AVP) can be generalized for other physiological response patterns. We therefore studied the vagal control of the endocrine pancreas during food intake. Young (3 months old) and aged (27 months old) male Wistar rats were provided with permanent cardiac catheters allowing free movement and repeated, stress-free blood sampling. The vagally mediated preabsorptive insulin response (PIR) in relation to food intake as seen in young rats was reduced in aged ones. Blood glucose increments were the same at both ages. Administration of Amph (0.5 mg/kg; s.c.) 30 min before, or AVP (10 micrograms/kg; s.c.) 60 min before presentation of a test meal led to an elevation of the magnitude of insulin secretion in young rats but reduced the response in aged rats. Moreover, the PIR was not reinstated in aged rats. Blood glucose increments were not influenced by the treatments. The results are interpreted in terms of age-related general reduction of parasympathetic reactivity. The differential effect of amphetamine and AVP treatment on the insulin response suggests that the central aminergic or peptidergic drive of vagal output to the endocrine pancreas is also age-related.

Aging↗

Stress and differential alterations in immune system functions: conclusions from social stress studies in animals.

Psychosocial factors are implicated in the development, in the course of, and in the recovery from disease. The immune system may be a mediator of the disease. Studies with animal models using social interactions in rodents suggest that short- and long-term social stress does not invariably suppress immune system functions. The magnitude and direction of changes in diverse compartments of the immune system are highly correlated to the social position of the animal. Furthermore, genetic, developmental, and adult experience may predetermine the animal's coping strategy both in terms of behaviour and neuroendocrinology, and hence in immunology as well. It is argued that disease processes should be considered as a function of baseline immunological state.

Adaptation, Psychological↗

Differential effect of lesioning of the central amygdala on the bradycardiac and behavioral response of the rat in relation to conditioned social and solitary stress.

The central nucleus of the amygdala (CEA) is considered to be involved in stress-dependent regulation of autonomic functions. In the present study the effects of a bilateral electrolytic lesion of the CEA on the cardiac response and on the duration of immobility behavior in two conditioned stress situations have been analysed in Wistar rats. Fear of a previously received electric footshock elicited in almost all animals a profound early bradycardia and a marked immobility behavior in comparison to non-stressed freely moving controls. Lesioning of the CEA completely abolished the bradycardiac response. Immobility behavior was slightly diminished. The conditioned fear of a dominant rat following social defeat was accompanied by a bradycardiac response in about 50% of the rats. This bradycardiac response was not accompanied by significant immobility behavior. The rest of the defeated rats--i.e. cardiac 'non-responders'--displayed an early increase in immobility behavior. The CEA lesion abolished again the bradycardiac response, but the immobility behavior remained unchanged. In the cardiac 'non-responders' CEA lesion failed to affect immobility behavior, and the heart rate also remained unchanged. These results suggest that the CEA is involved in the organization of conditioned parasympathetic responses independent of the nature of stress. In contrast, the role of this nucleus in the organization of the immobility behavior seems to depend on the nature of stress and other, probably individual characteristics of the rats' behavior.

Amygdala↗

The central amygdala is involved in the conditioned but not in the meal-induced cephalic insulin response in the rat.

The central nucleus of the amygdala (CEA) is considered to be involved in the regulation of autonomic correlates of fear. Its involvement in the control of autonomic functions other than elicited by fear has received little attention. The effects of a bilateral electrolytical lesion of the CEA on feeding related insulin responses have been analyzed in male Wistar rats. The cephalic phase of the insulin response is a vagally mediated elevation of plasma insulin concentration during the first minute after meal onset, before any increase in plasma glucose can be noticed. This response can also be entrained to environmental stimuli. The insulin response elicited under these conditions is due to conditioning. CEA lesioning abolished the conditioned insulin response but not the early insulin elevation during the presentation of food. The CEA lesion failed to affect plasma glucose levels in both the meal-induced and conditioned test situations. To our knowledge this is the first study that shows that the CEA is also involved in the organization of conditioned metabolic endocrine responses.

Amygdala↗

The effect of ipsapirone on behavioural and cardiac responses in the shock-probe/defensive burying test in male rats.

The effects of the 5-HT1A receptor agonist, ipsapirone, on cardiac and behavioural responses of male Wistar rats in a conditioned defensive burying paradigm for anxiolytics were investigated. The shocked rats displayed defensive burying accompanied by an increase in heart rate. Ipsapirone-treated rats (5 and 10 mg/kg i.p.) showed less burying behaviour than did vehicle-treated controls, and the tachycardiac response was also reduced in a dose-dependent way whereas eating behaviour was facilitated. The results demonstrate the effectiveness of ipsapirone, thereby suggesting the involvement of 5-HT1A receptors in a conditioned anxiety situation that elicits an active coping behaviour and sympathetic activation.

Animals↗

Anxiolytics and stress-induced behavioural and cardiac responses: a study of diazepam and ipsapirone (TVX Q 7821).

The present study has been designed to investigate the effects of the 5-HT1A receptor agonist, ipsapirone (TVX Q 7821), a representative of a novel class of anxiolytics, and the classical benzodiazepine anxiolytic, diazepam, on cardiac and behavioural responses in an emotional stress situation. The emotional stress of fear of punishment, induced by training male Wistar rats in an inhibitory avoidance situation, was followed by a bradycardiac response relative to similarly trained, but non-punished, freely moving rats. The behavioural response of stressed rats was immobility in the dark compartment in which an electric footshock (0.6 mA a.c. for 3 s) had been administered as punishment a day earlier. Diazepam administered i.p. in doses of 2.5 mg/kg and 7.5 mg/kg caused a decrease in the interbeat interval (IBI) in shocked and non-shocked rats whereas ipsapirone administered i.p. in doses of 2.5 and 12.5 mg/kg decreased the IBI in shocked rats only. Ipsapirone diminished the duration of immobility in both shocked and non-shocked animals whereas diazepam decreased immobility in shocked rats only. These results suggest a differential effect of the two anxiolytics on the behavioural and cardiac responses to an emotional stress situation. It is suggested that ipsapirone has an anxiolytic-like effect and 'anti-stress' action that is clearly reflected in the cardiac physiology in an anxiety-inducing situation.

Animals↗

Protective effect of the calcium antagonist nimodipine on discrimination learning deficits and impaired retention behavior caused by prenatal nitrite exposure in rats.

Discrimination learning behavior and retention of a passive avoidance response were studied in male adult offspring of gestating rats exposed to drinking water containing 2 g/l sodium nitrite, throughout the second half of pregnancy. Both in an auditory and visual discrimination learning paradigm NaNO2-exposed rats were inferior to controls. The long-term retention of a passive avoidance response was also impaired. The acquisition of simple learning tasks was not significantly disturbed. The concomitant prenatal daily treatment with the calcium antagonist nimodipine in a dose of 10 mg/kg p.o. interfered with the nitrite neurotoxicity and prevented the development of adult behavioral deficits. The results support the hypothesis that Ca2+ homeostasis of neurons is an important factor for normal development of brain and behavior.

Animals↗

Behavioral and neuroendocrine response to psychosocial stress in male rats: the effects of the 5-HT 1A agonist ipsapirone.

The effect of the 5-HT 1A agonist ipsapirone on the behavior, plasma catecholamine, and corticosterone levels was studied in male Wistar rats during the psychosocial stress of confrontation with a confined dominant opponent 24 hr after defeat. The effect of the drug was also studied during a predefeat confrontation with the confined (would-be dominant) rat. Blood samples were withdrawn via a permanent heart catheter. The drug (5 mg/kg, ip) or vehicle was given 30 min before transportation to the experimental room. Ipsapirone had no major effects on the plasma hormone concentrations and had no influence upon the behavioral response to the confined rat. At the postdefeat test ipsapirone led to a significant increase of immobility, whereas both rearing and time spent sniffing the cage were diminished. Postdefeat psychosocial stress resulted in an increase of the hormone, particularly catecholamine levels. These responses were further elevated by the drug. The presence of high corticosterone levels in the home cage after postdefeat ipsapirone treatment leads to the hypothesis that postsynaptic 5-HT 1A receptor hypersensitivity develops after the social stress of defeat.

Agonistic Behavior↗

Age-related alterations in cardiac response to emotional stress: relations to behavioral reactivity in the rat.

Age and behavioral characteristics are considered as risk factors for disturbances of the cardiac rhythm. Emotional stress may be a disseminating factor. Therefore, cardiac responsiveness and behavioral reactivity and their relation as a function of age have been studied in the rat. Young (3-month-old) and young adult (5-month-old) rats display a relative deceleratory cardiac response with bradyarrhythmias in the initial phase of response to emotional stress evoked by stimuli associated with a previous painful experience. The behavioral response is immobility. The immobility response is also displayed by aged (21-month-old) and senescent (33-month-old) rats but the initial bradycardiac heart response to emotional stress is absent, and the incidence of repetitive extrasystoles is increasing with age. An inverse correlation between behavioral reactivity to novel stimuli and the bradycardiac heart responsiveness is observed in young and young adult individual animals. The behavioral reactivity of the aged and senescent rats is diminished, but the correlation with cardiac reactivity remains preserved. It is suggested that the behaviorally coupled inhibitory influences on the heart are diminishing during aging either due to impairments in the descending cholinergic (vagal) system or secondarily, due to a decrease in the central "drive" of this system.

Aging↗

Effects of amphetamine and beta-endorphin fragments on maze performance in rats.

Fragments of beta-endorphin and amphetamine cause similar effects in some tests of maze behavior in rats. The present study served to compare the influence of amphetamine and two beta-endorphin fragments [beta-endorphin (beta E)-(2-9) and beta E-(2-16)] on maze behavior in more detail. In Experiment I no significant effects of amphetamine and the peptides on behavioral performance in three selected Davenport configurations were found. In Experiment II amphetamine increased the frequency of errors and of returns to the start box, but only in the first trial. This effect was dependent on the rats' experience and on the maze configuration. In the next 11 trials, amphetamine slightly decreased the overall frequency of errors and of returns to the start box. Therefore, the effects of amphetamine on maze behavior depend upon the extent of training experience and on the structure of the test mazes. The peptides did not significantly affect maze performance. It is concluded that the effects of amphetamine and the beta-endorphin fragments on maze behavior are not comparable in this maze test.

Animals↗

Behavioural physiology of serotonergic and steroid-like anxiolytics as antistress drugs.

Pharmacological studies are useful tools to understand the neurobiological basis of behavioural and physiological stress mechanisms. Ipsapirone, a 5-HT1A autoreceptor agonist is a representative of novel anxiolytics without the disadvantages of benzodiazepam-like drugs. Behavioural, physiological and neuroendocrine studies in the rat are reviewed which were aimed to investigate the antistress properties of ipsapirone during reexposure to various conditioned emotional stress situations. It is demonstrated that in certain situations, probably due to a stress-induced sensitisation of postsynaptic 5-HT1A receptors, anxiolytic doses of the drug may show prostress (anxiogenic) behavioural and neuroendocrine effects. Furthermore, brain corticosteroid receptors, probably interacting with the serotonergic transmission, are involved in anxiogenic/prostress processes. In this respect antagonists of the brain mineralocorticoid-like (type I) receptors may be important antistress drugs of the future.

Animals↗

Behavioral and cardiac responses to a sudden change in environmental stimuli: effect of forced shift in food intake.

In order to test the possibility of a change in stress susceptibility induced by a forced change in activity rhythm, during control weeks food availability was restricted to the dark period only (fa-D) and to the light period only during the test week (fa-L). Stress susceptibility was measured on the basis of the decrease in heart rate (bradycardia) and an increase in freezing behavior in response to a sudden reduction in background noise. A significant increase in bradycardia both in magnitude and duration was observed during fa-L conditions as compared to the control fa-D condition. Also the duration of freezing behavior was increased during the fa-L condition. These results support the hypothesis that forced changes in circadian activities affect stress susceptibility. The significance of this finding for the incidence of stress pathologies is discussed.

Activity Cycles↗