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Biomedical subjects

J M Koolhaas

Publications and source records attributed to J M Koolhaas.

At least 91 records · Page 5Linked to original sources

Cardiac, neuroendocrine, and behavioral effects of central amygdaloid vasopressinergic and oxytocinergic mechanisms under stress-free conditions in rats.

The central nucleus of the amygdala (CEA) is considered to play a major role in the expression of behavioral, autonomic, and neuroendocrine components of the stress response. The present study was designed to examine possible modulating effects of the neuropeptides arginine-8-vasopressin (AVP) and oxytocin (OXT) on functioning of the CEA in male Wistar rats. Heart rate, neuroendocrine parameters, and behavioral activity were repeatedly measured before, during, and after local administration of several doses of AVP and OXT under stress-free resting conditions. In comparison with control artificial-CSF infusion, AVP infusion in the lowest dose (20 pg) caused in a part of the animals a long-lasting decrease in heart rate, i.e., bradycardia, without affecting behavioral activity. In contrast, local infusion with high doses of AVP and OXT (2 ng) induced a transient cardioacceleration concomitant with an increase in behavioral activity. Moreover, these latter effects of AVP could effectively be blocked by pretreatment with a selective OXT receptor antagonist. These findings suggest that higher doses of AVP are effective via agonistic action on OXT receptors in the CEA. A strong correlation existed between the magnitudes of the tachycardiac response and behavioral activation. Thus, heart rate increase by OXT receptor stimulation is possibly due to somatic-autonomic coupling rather than genuine autonomic activation. Additionally, plasma corticosterone, but not epinephrine and norepinephrine, concentrations were elevated in response to AVP and OXT infusions. In conclusion, these results suggest that vasopressinergic influences on CEA function involve two receptor mechanisms possibly related to differential output systems.

Amygdala↗

Social conflict situations in rats differentially affect the development of amygdala kindling.

Clinical studies revealed an association between the occurrence of convulsions and stress. However, the direction of such relations and their mechanisms are not quite clear. The present study investigated the influence of stress-inducing agonistic conflict situations on the progressive process of kindling epileptogenesis induced by daily tetanic stimulation of the amygdala. Whereas repeated exposure to defeat in an agonistic setting did not affect the development of amygdala kindling, repeated victory experiences resulted in a significant retardation of the kindling process. Moreover, the kindling process was retarded to a greater extent in rats that quickly displayed offensive behavior and won the confrontation. Possible underlying mechanisms and biological substrates are discussed in terms of the ability of the individual to control or cope with the nature of the stressor.

Amygdala↗

Posttraining norepinephrine infusion into the central amygdala differentially enhances later retention in Roman high-avoidance and low-avoidance rats.

Memory-enhancement effects of norepinephrine (NE) were investigated by infusing NE into the central amygdala (CEA) of Roman high-avoidance (RHA) and low-avoidance (RLA) rats after training on active and passive behaviors in the defensive-burying paradigm. During acquisition, both lines spent comparable time in burying behavior. RLA rats, but not RHA rats, also displayed substantial immobility. During retention, the cerebrospinal-fluid-treated RLA rats mostly displayed immobility to the nonelectrified probe, whereas the RHA rats showed neither burying nor immobility. In the RLA rats, high-dose (200 ng), but not low-dose (20 ng), NE infusion enhanced the duration of the passive response (immobility) without affecting the active response. NE given into the CEA of RHA rats caused a selective dose-dependent appearance of the active behavioral component. The results suggest a phenotype-dependent effect of intra-amygdaloid NE on memory processes in the rat.

Amygdala↗

Immunological responses to social stress: dependence on social environment and coping abilities.

Social interactions as a consequence of the social position represent stressful conditions for the individual. Manipulation of social conditions or forming long-term social hierarchies by colony aggregation allow to investigate the regulation of immune defense mechanisms under seminatural circumstances. The present paper describes the effects of dyadic social interaction in male rats with or without direct aggressive interactions on some indices of humoral and cellular immunity. In addition, for comparative and reference purposes, in one experiment the conventional stressor of inescapable footshock was used as well. Primary humoral immune response to sheep red blood cell antigen is suppressed by repeated experience of both defeat and inescapable footshock. At individual level the social stressor is as effective as the conventional stressor of inescapable footshock, less individual rats show suppression following the social than after the conventional stress. The social stressors, i.e. being exposed to a resident or intruder of the territory, facilitate lymphocyte proliferation in the spleen by the mitogen ConA and PHA independently of the presence or absence of direct aggressive interaction. Finally, the different social stressors have some impact on the lymphocyte subpopulation in the spleen. Social stimulation without aggressive interactions increases the relative number of T-helper cells, whereas defeat leads to an increase in the T-suppressor/cytotoxic subpopulation. The data suggest multiple and differential effects of social stress on immune system functioning in the rat. Individual characteristics of the coping with stress, the social environment, and the immune indices under investigation determine the magnitude and direction of the changes in immune functioning.

Adaptation, Psychological↗

Vasopressinergic modulation of stress responses in the central amygdala of the Roman high-avoidance and low-avoidance rat.

The central nucleus of the amygdala (CEA) is selectively involved in the passive component of the behavioral (immobility) and the accompanying parasympathetic response during conditioned, stressful environmental challenges. Vasopressinergic mechanisms in the brain seem to play a role in these stress responses. The effects of the neuropeptides arginine-8-vasopressin (AVP) and oxytocin (OXT) on modulating CEA activity during conditioned stress of inescapable footshock were studied in male Roman high-avoidance (RHA/Verh) and low-avoidance (RLA/Verh) rats, psychogenetically selected on the basis of shuttle-box acquisition behavior. In RLA/Verh rats, the cardiac and behavioral responses to the conditioned emotional stressor were bradycardia and immobility, suggesting an important role for the CEA in these rats. The RHA/Verh rats, however, failed to show any change in heart rate or immobility in response to a conditioned stress situation. The low dose of AVP (20 pg) in the CEA of conscious RLA/Verh rats caused an enhancement of the stress-induced bradycardiac and immobility response. However, the high dose of AVP (2 ng) and OXT (200 pg) attenuated the bradycardiac and immobility responses in the RLA/Verh rats. Infusion of AVP and OXT in the RHA/Verh rats failed to induce any change in heart rate or immobility. Binding studies revealed that the AVP receptor selectively binds AVP with high affinity. In contrast, the OXT receptor recognizes both AVP and OXT with a similar (but lower) affinity. This suggests that the behavioral and autonomic responses of the high dose of AVP may be caused by OXT receptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗

Effect of different agonistic experiences on behavioural seizures in fully amygdala kindled rats.

Fully amygdala kindled rats were exposed to two different inter-male agonistic experiences in order to study the interaction between epilepsy and acute social stress. Victory experience did not influence the severity of seizure behaviour, whereas a single acute defeat modified both ictal and postictal seizure manifestations. Defeat resulted in less severe and shorter lasting motor seizures, and the accompanied postictal inhibition or behavioural depression was of shorter duration in comparison with pre-stress values. The ability of acute defeat to trigger anticonvulsant activity as implied by the weakened convulsive response is discussed.

Agonistic Behavior↗

Conditioned neuroendocrine and cardiovascular stress responsiveness accompanying behavioral passivity and activity in aged and in young rats.

Mean arterial pressure (MAP), heart rate (HR), plasma epinephrine (E), plasma norepinephrine (NE), and plasma corticosterone (CORT) were measured in 3-month- and 24-month-old male Wistar rats exposed to a conditioned emotional stress response (CER) paradigm and a conditioned defensive burying (CDB) paradigm. In the CER situation blood samples were taken during reexposure to the training environment one day after a single inescapable footshock (0.6 mA, AC for 3 s) had been administered. In the CER paradigm the young rats displayed passive behavior (immobility) accompanied by an increase in plasma levels of CORT and E, whereas both the control and conditioned animals showed increased NE responses. Previously shocked aged rats exhibited an attenuated plasma NE response, whereas levels of E remained elevated to a greater extent. Aged animals showed elevated basal levels of CORT one day after footshock administration. Stress-induced immobility was preserved in the aged rats. These animals had an increase in basal MAP values and a decrease in basal HR values compared to young ones. In the CDB paradigm, rats were exposed to a nonelectrified probe 1 day after the repeated shock (2 mA/contact) procedure. Young rats displayed defensive burying accompanied by increments in MAP, HR, CORT, and NE. The aged animals showed similar hormonal, autonomic, and behavioral stress responses. Thus, the age-related alterations in neuroendocrine and autonomic response patterns are apparent in stressed animals during behavioral passivity in absence of control (CER) rather than during active control (defensive burying).

Adaptation, Psychological↗

Behavioral and cardiac responses to mild stress in young and aged rats: effects of amphetamine and vasopressin.

Young (3-month-old) male Wistar rats showed a relative decrease in heart rate to a sudden silence superimposed on low intensity background noise. This bradycardia was accompanied by immobility behavior. In 26-month-old rats the magnitude of the heart rate response was reduced while immobility behavior remained in the same order of magnitude as in young controls. In the aged rats a shift in autonomic regulation of heart rate in the direction of increased sympathetic influence was indicated by the results obtained by blocking the autonomic input with atropine methyl-nitrate (0.5 mg/kg) or atenolol (1 mg/kg) given subcutaneously (SC) 30 min prior to testing. Pretest (30 min) administration of amphetamine (0.5 mg/kg SC) reinstated the bradycardiac response in aged rats to a level seen in young ones. Arginine-vasopressin (AVP, 10 micrograms/kg SC), administered 60 min before the experiment, markedly facilitated the cardiac response in young animals but failed to restore cardiac responses in aged ones. The immobility behavior in the peptide-treated aged rats was also absent. The present findings suggest that a diminished central aminergic drive in aged rats is causing a reduction of the parasympathetic cardiac response to stress of sudden silence. The results also indicate an age-related vasopressinergic modulation of behavioral and cardiac responses to mild stress.

Aging↗

Differential effects of neonatal testosterone treatment on aggression in two selection lines of mice.

Selection lines of mice, artificially selected for aggression based upon the attack latency score (ALS), were used. In order to determine the relative contribution of neonatal testosterone (T) in the development of aggression, we vary the plasma-T level in males of both selection lines on the day of birth. At 14 weeks the ALS was measured. Neonatal T treatment results in a reduction of aggression in the long attack latency (LAL) line, whereas aggressive behaviour of the short attack latency (SAL) line is not affected. Both selection lines show reduction in testicular weight, although the total amount of T-producing Leydig cells was not affected. Neonatal T may cause a permanent reduction in aggressive behaviour in in the LAL line only, probably due to differential appearance of critical periods. It is suggested that the difference in aggressive behaviour between SAL and LAL selection lines is due to a prenatally determined difference in neonatal T sensitivity of the brain.

Aggression↗

Neuroendocrine and behavioral responses during conditioned active and passive behavior in the defensive burying/probe avoidance paradigm: effects of ipsapirone.

Plasma epinephrine (E), norepinephrine (NE), and corticosterone (CORT) concentrations were determined in the rat before, during, and after a 15-min exposure to a nonelectrified probe on day after receiving electric shock (1.5 mA) through a probe mounted on the wall of the home cage. Rats displayed burying (active coping) if sawdust was provided on the floor and immobility (passive coping) if bedding was absent both during training and testing. The conditioned burying was accompanied by high plasma NE but low E and CORT concentrations, whereas immobility was associated with high CORT and low NE levels. A forced switch from the active to passive coping (training with and testing without sawdust) led to the highest rise in E concentration. The 5-HT1A agonist ipsapirone, with anxiolytic properties, dose-dependently (0.5 and 2.5 mg/kg, IV) reduced defensive burying behavior and increased the amount of time spent on feeding behavior in the presence of bedding material. Both plasma E and CORT levels were further elevated by the higher dose of ipsapirone. In the absence of bedding material, ipsapirone failed to affect immobility behavior, but it dose-dependently elevated the stress-induced increase in E, NE, and CORT concentrations. Accordingly, the behavioral anxiolytic action of the 5-HT1A agonist ipsapirone was restricted to active coping, whereas neuroendocrine activation by the drug was present in all conditions. It is suggested that the effects of ipsapirone on behavioral coping and neuroendocrine regulation are produced by different populations of 5-HT1A receptors in the brain.

Animals↗

Vasopressin prolongs behavioral and cardiac responses to mild stress in young but not in aged rats.

In young male Wistar rats sudden silence superimposed on low intensity background noise evokes a relative decrease in heart rate. This bradycardia is accompanied by immobility behavior. In the present study, involving young (3 month), late-adult (14 month), aged (20 month), and senescent (25 month) rats the magnitude of the stress-induced bradycardia shows an age-related reduction while the behavioral immobility response remained unchanged during the process of aging. Arginine-8-vasopressin (AVP, 6 micrograms/kg SC) administered 60 min prior to the experiment led to a prolonged behavioral and cardiac stress response in young and late-adult rats, but not in aged and senescent animals. The peripheral and central mechanisms possibly involved in the failure of systemically applied AVP to improve bradycardiac stress responses in aged rats are discussed.

Aging↗

Corticosteroid receptor plasticity in the central nervous system of various rat models.

The action of corticosteroids in the central nervous system (CNS) is mediated by two distinct corticosteroid receptors: the mineralocorticoid and glucocorticoid receptors (MR and GR respectively). Using an established in vitro binding assay system, MR and GR binding parameters were determined in the hippocampal, hypothalamic and pituitary cytosol of various rat models. In the (pharmaco-)genetically selected rat lines, the apomorphine susceptible (APO-SUS) rats showed a significant increase in the hippocampal and pituitary MR binding capacities (but not affinity) compared to those in the apomorphine-unsusceptible (APO-UNSUS) rats. In immunologically-altered Lewis (LEW/N) rats and in spontaneously hypertensive rats (SHR), increased hippocampal MR capacity (but not affinity) and hypothalamic MR capacity were observed compared to their respective control, Wistar (WIST) and Wistar Kyoto (WKY) rats. In addition, compared to WKY rats, SHR rats also showed a much greater pituitary but lesser hypothalamic GR binding capacity. In rats subjected to alteration in environmental conditions, the long-term effects of a short inescapable stress resulted in a significant increase in both hippocampal MR and GR while the pituitary and hypothalamic MR and GR do not differ in the stress and control groups. In rats subjected to a defeat test, a decrease in hippocampal MR and GR was observed 3 weeks (but not 1 week) later.

Animals↗

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↗