Psychobiological evidence of the stress resilience fostering properties of a cosmetic routine.

Everyday life psychosocial stressors contribute to poor health and disease vulnerabilty. Means alternative to pharmacotherapy that are able to foster stress resilience are more and more under the magnifying glass of biomedical research. The aim of this study was to test stress resilience fostering properties of the self-administration of a cosmetic product enriched with essential oils. On day 0, fourty women, 25-50 years old, self-administered both the enriched cosmetic product (ECP) and a placebo one (PCP). Then, women were randomized for daily self-administration (from day 1 to 28) of either ECP (n = 20) or PCP (n = 20). On day 29, subjects underwent a psychosocial stress test (PST). Autonomic (heart rate and its variability) and neuroendocrine (salivary cortisol) parameters were assessed both on day 0 and 29. All subjects filled a number of psychological questionnaires in order to quantify anxiety, perceived stress, and mood profile, and were videorecorded during PST for non-verbal behavior evaluation. A single application of ECP produced an acute potentiation of cardiac parasympathetic modulation, which was not observed when placebo was used. Prolonged self-administration of ECP induced: (i) a dampening of the cortisol rise produced by PST, (ii) a reduction of state anxiety, (iii) a favorable change in mood profile, and (iv) a reduction of non-verbal behavior patterns that signal anxiety, motivational conflict and avoidance. In conclusion, this study suggests that the self-administration of a cosmetic cream enriched with essential oils should be considered as a stress resilience fostering strategy due to its favorable physiological, neuroendocrine and psychological effects.

Effect of anisotropy on ventricular vulnerability to unidirectional block and reentry by single premature stimulation during normal sinus rhythm in rat heart.

Single high-intensity premature stimuli when applied to the ventricles during ventricular drive of an ectopic site, as in Winfree's "pinwheel experiment," usually induce reentry arrhythmias in the normal heart, while single low-intensity stimuli barely do. Yet ventricular arrhythmia vulnerability during normal sinus rhythm remains largely unexplored. With a view to define the role of anisotropy on ventricular vulnerability to unidirectional conduction block and reentry, we revisited the pinwheel experiment with reduced constraints in the in situ rat heart. New features included single premature stimulation during normal sinus rhythm, stimulation and unipolar potential mapping from the same high-resolution epicardial electrode array, and progressive increase in stimulation strength and prematurity from diastolic threshold until arrhythmia induction. Measurements were performed with 1-ms cathodal stimuli at multiple test sites (n = 26) in seven rats. Stimulus-induced virtual electrode polarization during sinus beat recovery phase influenced premature ventricular responses. Specifically, gradual increase in stimulus strength and prematurity progressively induced make, break, and graded-response stimulation mechanisms. Hence unidirectional conduction block occurred as follows: 1) along fiber direction, on right and left ventricular free walls (n = 23), initiating figure-eight reentry (n = 17) and tachycardia (n = 12), and 2) across fiber direction, on lower interventricular septum (n = 3), initiating spiral wave reentry (n = 2) and tachycardia (n = 1). Critical time window (55.1 ± 4.7 ms, 68.2 ± 6.0 ms) and stimulus strength lower limit (4.9 ± 0.6 mA) defined vulnerability to reentry. A novel finding of this study was that ventricular tachycardia evolves and is maintained by episodes of scroll-like wave and focal activation couplets. We also found that single low-intensity premature stimuli can induce repetitive ventricular response (n = 13) characterized by focal activations.NEW & NOTEWORTHY We performed ventricular cathodal point stimulation during sinus rhythm by progressively increasing stimulus strength and prematurity. Virtual electrode polarization and recovery gradient progressively induced make, break, and graded-response stimulation mechanisms. Unidirectional conduction block occurred along or across fiber direction, initiating figure-eight or spiral wave reentry, respectively, and tachycardia sustained by scroll wave and focal activations.

Early maternal separation has mild effects on cardiac autonomic balance and heart structure in adult male rats.

Early life adverse experiences have long-term physiologic and behavioral effects and enhance stress sensitivity. This study examined the effects of maternal separation (MS) on cardiac stress responsivity and structure in adulthood. Male Wistar rats were separated from the dams for 3 h per day from postnatal days 2 through 15. When exposed to 5-day intermittent restraint stress (IRS) as adults, MS, and control rats showed similar acute modifications of cardiac sympathovagal balance, quantified via heart rate variability analysis. In addition, MS had no effect on cardiac pacemaker intrinsic activity (as revealed by autonomic blockade with scopolamine and atenolol) and did not affect the circadian rhythmicity of heart rate, neither before nor after IRS. However, MS differed from control rats in cardiac parasympathetic drive following IRS, which was heightened in the latter but remained unchanged in the former, both during the light and dark phases of the daily rhythm. The evaluation of adult cardiac structure indicated that stress experienced during a crucial developmental period induced only modest changes, involving cardiomyocyte hypertrophy, increased density of vascular structures, and myocardial fibrosis. The mildness of these functional-structural effects questions the validity of MS as a model for early stress-induced cardiac disease in humans.

Antioxidant amelioration of dilated cardiomyopathy caused by conditional deletion of NEMO/IKKgamma in cardiomyocytes.

RATIONALE: Insight into the function of nuclear factor (NF)-kappaB in the adult heart has been hampered by the embryonic lethality of constitutive NF-kappaB inactivation. OBJECTIVE: The goal of the present study was therefore to gain insights into the role of NF-kappaB pathway specifically in mouse cardiomyocytes by conditional deletion of the NF-kappaB essential modulator (NEMO). METHODS AND RESULTS: Using a Cre/loxP system, we disrupted the Nemo gene in a cardiomyocyte-specific manner in the heart, which simulated gene expression changes underlying human heart failure and caused adult-onset dilated cardiomyopathy accompanied by inflammation and apoptosis. Pressure overload challenges of NEMO-deficient young hearts precociously induced the functional decrements that develop spontaneously in older knockout animals. Moreover, oxidative stress in NEMO-deficient cardiomyocytes is a critical pathological component that can be attenuated with antioxidant diet in vivo. CONCLUSIONS: These results reveal an essential physiological role for NEMO-mediated signaling in the adult heart to maintain cardiac function in response to age-related or mechanical challenges, in part through modulation of oxidative stress.

Dependence of temporal variability of ventricular recovery on myocardial fibrosis. Role of mechanoelectric feedback?

OBJECTIVE: The study was aimed at establishing the effect of factors involved in the expression of mechanoelectric feedback in the heart, such as R-R interval and connective tissue, on time dependent changes in ventricular recovery, as determined at the body surface by beat to beat variability of QRST integral maps (BBV-IM). METHODS: We used 15 normal 6-month-old Wistar rats. In each anesthetized animal, we performed a 3-minute continuous recording of 44. The simultaneous chest ECGs. The signals were interactively processed, 1) to determine mean R-R interval and R-R variability throughout the recording period and 2) to compute QRST integral maps from approximately 50 beats belonging to the end of expiration. Then BBV-IM was calculated and expressed as percentage of beats significantly differing from a template. At sacrifice, the amount of myocardial fibrosis was morphometrically evaluated. RESULTS: R-R interval was 149 ms +/- 4, R-R interval variability 0.008 +/- 0.001 and BBV-IM 30.7% +/- 4.4. Myocardial fibrosis expressed as % volume of left ventricular myocardium, numerical density of fibrotic foci and average cross-sectional area of the foci was 3.0% +/- 0.4, 3.8 +/- 0.6 and 4.4 microns(2)/1000 +/- 0.1 respectively, BB-IM was positively correlated to the % volume of fibrosis (r = 0.83, P < 0.0003). Both measurements were positively correlated to R-R interval (BBV-IM: r = 0.83, P < 0.0001; % volume of fibrosis: r = 0.87, P < 0.001) and negatively correlated to cardiac weights (BBV-IM: r = -0.79, P < 0.0005; % volume of fibrosis: r = -0.75, P < 0.001). CONCLUSION: Beat to beat changes in ventricular repolarization attributable to mechanoelectric transduction can be detected at the body surface by means of BBV-IM.

Social stress, autonomic neural activation, and cardiac activity in rats.

Animal models of social stress represent a useful experimental tool to investigate the relationship between psychological stress, autonomic neural activity and cardiovascular disease. This paper summarizes the results obtained in a series of experiments performed on rats and aimed at verifying whether social challenges produce specific modifications in the autonomic neural control of heart rate and whether these changes can be detrimental for cardiac electrical stability. Short-term electrocardiographic recordings were performed via radiotelemetry and the autonomic input to the heart evaluated by means of time-domain heart rate variability measures. Compared to other stress contexts, a social defeat experience produces a strong shift of autonomic balance toward sympathetic dominance, poorly antagonized by vagal rebound, and associated with the occurrence of cardiac tachyarrhythmias. These effects were particularly severe when a wild-type strain of rats was studied. The data also suggest that the cardiac autonomic responses produced by different types of social contexts (dominant-subordinate interaction, dominant-dominant confrontation, social defeat) are related to different degrees of emotional activation, which in turn are likely modulated by the social rank of the experimental animal and the opponent, the prior experience with the stressor, and the level of controllability over the stimulus.

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.

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.

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.

Individual differences in plasma catecholamine and corticosterone stress responses of wild-type rats: relationship with aggression.

Plasma noradrenaline (NA), adrenaline (A), and corticosterone (CS) responses to social and nonsocial stressors were studied in male members of a strain of wild-type rats, widely differing in their level of aggression. The aggressiveness was preliminarily established by measuring the latency time to attack (ALT) a male intruder in a standard resident-intruder test. Animals were then provided with a jugular vein cannula for blood sampling during stress exposure. Implanted rats were randomly assigned to 3 experimental treatments: social stress (defeat experience, SD), nonsocial stress (presentation of a shock-prod, SP) and control (animals undisturbed in their home cages, CTR). A significant correlation was found between ALT and the amount of time spent in burying the probe in SP rats: the more aggressive the animal, the higher the rate of burying behavior. SD induced a much stronger effect on plasma NA, A, and CS concentrations than SP. A significant negative correlation was found between ALT scores and values of the area under the response time curve for NA and A, in both SD and SP situations: the more aggressive the animal, the higher the catecholaminergic reactivity to the stressors. On the contrary, no evidence of a correlation between aggressiveness and plasma corticosterone responses was found, neither in SD nor in SP rats. These findings in an unselected strain of wild-type rats confirmed that an aggressive/active coping strategy is associated with a high sympathetic-adrenomedullary activation and support the concept of individual differentiation in coping styles as a coherent set of behavioral and neuroendocrine characteristics.

Behavioral and electrocardiographic responses to social stress in male rats.

Telemetry ECGs were recorded from Wistar male rats during social stress induced by exposure to aggressive lactating female rats. Behavioral response to maternal attack was evaluated in terms of relative duration of passive submissive (p/s) and active/nonsubmissive (a/ns) patterns. A decrease of R-R interval (R-R) compared to baseline conditions was found, significantly more pronounced than that observed in control animals exposed just to novel environment. R-R variability during social stress was positively correlated with the amount of p/s behavior. R-R fluctuations, episodes of II degree A-V block, and ventricular arrhythmias were also observed. Most R-R fluctuations and II degree A-V blocks were temporally associated with phases of p/s behavior and periods of high R-R variability. Ventricular arrhythmias generally appeared during a/ns behavior and were temporally linked with periods of low R-R variability. Ventricular arrhythmias, low R-R variability, and concomitant a/ns behavior might be related to an increased sympathetic activity. R-R fluctuations and II degree A-V blocks, associated with high R-R variability and p/s behavior, might be related to a predominant inhibitory effect of vagal activation (accentuated antagonism).

Electrode positioning for reliable telemetry ECG recordings during social stress in unrestrained rats.

We describe a surgical procedure for optimizing the location of telemetry ECG leads in rats. The new location was aimed at obtaining an accurate representation of ECG features throughout the cardiac cycle by limiting the voltage instability usually observed during intense somatomotor activity and improving the signal-to-noise ratio. The two electrodes (wire loops) were fixed on the dorsal surface of the xiphoid process and in the anterior mediastinum close to the right atrium. The implantation procedure was fast, little invasive, and allowed animals to completely recover from intervention. The performance of the "improved" location (IL, n = 10) with respect to two subcutaneous (SC) positionings ("conventional positioning" CSP, n = 5; "updated location," USL, n = 5) was evaluated by comparing ECGs obtained in baseline, stress and recovery conditions and during different behavioral activities (immobility and grooming). The resident-intruder test (emotional/physical challenge) was chosen as experimental stress paradigm. The noise level of ECGs obtained from IL rats was lower than in CSP and USL animals, in all recording conditions. Percentages of correctly recognized beats (CRBs) over the total number of beats (TBs) were significantly higher in IL rats than in CSP and USL animals, both in baseline conditions (99% vs. 11% and 40%) and situations involving high somatomotor activity (stress: 97%, 5% and 16% recovery; 97%, 7% and 15%) (p < 0.01). The performance of IL as compared to CSP and USL was also better when percentages during grooming and immobility were considered (grooming: 93% vs. 4% and 23%: immobility: 97%, 6%, and 33%; p < 0.01).

Social stress, myocardial damage and arrhythmias in rats with cardiac hypertrophy.

In rat models of cardiac hypertrophy (moderate aortic coarctation: ACm, n=18; severe aortic coarctation: ACs, n=27; aging: OLD, n=25; spontaneous chronic hypertension: SHR, n=18) and properly matched control animals (C(ACm), n=17; C(ACs), n=19; C(OLD), n=24; C(SHR), n=22), we investigated the relative contribution of intense autonomic activity and cardiac structural damage to ventricular arrhythmogenesis. We used an "in vivo" to tissue level approach, by correlating in the same animal: (i) social stress-induced ventricular arrhythmias, telemetrically recorded, and (ii) left ventricular weights (LVW) and amount and geometrical properties of myocardial fibrosis (MF). Arterial blood pressure was significantly higher in ACm (+11%), ACs (+28%) and SHR (+34%) than in controls. LVW were approximately 20% greater in ACm, ACs and OLD and 50% greater in SHR. MF was about twice as great and characterized by more frequent occurrence of microscopic scarring in ACm and ACs, and eight times greater and associated with both a higher number and a larger size of fibrotic foci in OLD and SHR compared to controls. Social stress increased ventricular arrhythmia vulnerability in all models of cardiac hypertrophy, as well as in controls. The arrhythmogenic action of stress was facilitated in ACs, OLD and SHR. A correlation between structural cardiac remodeling and ventricular arrhythmias was found only in SHR and OLD, which exhibited the greatest increase in LVW and/or MF. Social stress proved to be a valuable tool for analyzing the combined effects of autonomic stimulation and altered myocardial substrate on the genesis of potentially life-threatening arrhythmias in social animals.

Cardiac autonomic responses to intermittent social conflict in rats.

Intermittent exposure to the same stressor can lead to a gradual decline in physiological, neuroendocrine and behavioral stress responses (habituation). We investigated possible habituation of cardiac autonomic responsiveness and susceptibility to cardiac arrhythmias in male rats exposed to either intermittent social victory (VIC) or defeat (DEF) stress (10 exposures in each case). Electrocardiograms were recorded via radiotelemetry and the sympathovagal balance at the level of the heart was evaluated via time-domain measurements of heart rate variability, namely average R--R interval (average time interval between two consecutive heart beats, RR), the standard deviation of RR (SD(RR)) and the root-mean-square of successive R--R interval differences (r-MSSD). Values of these parameters were significantly lower in DEF as compared to VIC rats in the second part of the test period (from Minute 6 to Minute 15), suggesting a more pronounced sympathetic dominance in the former group of animals. Accordingly, the occurrence of the most frequent cardiac arrhythmias (ventricular and supraventricular premature beats) was higher in DEF rats. Habituation of cardiac autonomic responsivity was observed across repeated exposure to victory, both in terms of sympathovagal balance and susceptibility to cardiac tachyarrhythmias, whereas no habituation was found in repeatedly defeated animals. A possible explanation to this discrepancy could be the different degree of controllability characterizing the two social challenging situations.

Maternal influences on food preferences in weanling mice Mus domesticus.

This study has been designed to evaluate the role of social (maternal) influences on the development of feeding behaviour in mice. A large enclosure, allowing direct observation, was divided into three separate areas: a central area for the nest and two side feeding areas at opposite ends. In one the young could feed with their mother, in the other one the young had to feed on their own. Three different groups were studied: one had the same food in the two feeding areas: the second had a less palatable food in the mother feeding area: the third had two different kinds of food with similar palatability in the feeding areas. The development of infants' behaviour expressed as: a) order of exit from the nest; b) first direction taken on leaving the nest; c) first food consumed: d) frequency of contacts with mother or pup food was electronically recorded and analysed. The results clearly show that weanling mice strongly prefer to follow their mother at her feeding sites even when the mother's food is less palatable than their own. Furthermore infants of one group, in a following binary choice test, preferred to eat the food they experienced in the mum's feeding area instead of what they experienced in their own feeding area. The fitness of such behaviour in more natural situations is discussed.

High carbon dioxide tension (PCO2) and the incidence of cardiac arrhythmias in rapidly growing broiler chickens.

The purpose of this investigation was to determine whether two-week-old rapidly growing broiler chickens with high metabolic activity have an increased risk of the development of heart failure three to five weeks later. The incidence of cardiac arrhythmias was assessed in broiler chickens with either a relatively high carbon dioxide tension (PCO2) or a low PCO2 in their venous blood. Their electrocardiograms (ECGS) were measured when the birds were between five and seven weeks old by means of a biotransplant which allowed them to move freely. Premature ventricular beats were observed in all the birds, but the largest numbers were observed in birds that had had a high PCO2 when they were two weeks old.

Social defeat and isolation induce clear signs of a depression-like state, but modest cardiac alterations in wild-type rats.

Adverse social environments play a relevant role in the onset and progression of mood disorders. On the other hand, depression is an independent risk factor for cardiovascular morbidity. This study was aimed at (i) corroborating the validity of a rat model of depression based on a negative social episode followed by social isolation and (ii) verifying its impact on cardiac function and structure. Pair housed, wild-type Groningen rats (Rattus norvegicus) were implanted with radiotransmitters for ECG, temperature and activity recordings. They were either exposed to a social defeat episode followed by 4-week isolation or left undisturbed with their female partners. The social challenge induced a series of biological changes that are commonly taken as markers of depression in rats, including decreased body weight gain and reduced preference for sucrose consumption, functional and structural changes of the hypothalamic-pituitary-adrenocortical axis, increased anxiety in the elevated plus maze test. The cardiovascular alterations consisted in (i) transitory heart rate circadian rhythm alterations, (ii) lack of habituation of cardiac autonomic responsivity (tachycardia and vagal withdrawal) to an acute stressor, and (iii) moderate hypertrophy affecting the right ventricle of the heart. These results indicate that a depression-like state induced via this model of social challenge was associated with a few modest cardiovascular changes. Further studies are required to confirm the validity of this rat model of depression as a valid preclinical approach to the comprehension of the biological substrates underlying depression-cardiovascular comorbidity.

Stress revisited: a critical evaluation of the stress concept.

With the steadily increasing number of publications in the field of stress research it has become evident that the conventional usage of the stress concept bears considerable problems. The use of the term 'stress' to conditions ranging from even the mildest challenging stimulation to severely aversive conditions, is in our view inappropriate. Review of the literature reveals that the physiological 'stress' response to appetitive, rewarding stimuli that are often not considered to be stressors can be as large as the response to negative stimuli. Analysis of the physiological response during exercise supports the view that the magnitude of the neuroendocrine response reflects the metabolic and physiological demands required for behavioural activity. We propose that the term 'stress' should be restricted to conditions where an environmental demand exceeds the natural regulatory capacity of an organism, in particular situations that include unpredictability and uncontrollability. Physiologically, stress seems to be characterized by either the absence of an anticipatory response (unpredictable) or a reduced recovery (uncontrollable) of the neuroendocrine reaction. The consequences of this restricted definition for stress research and the interpretation of results in terms of the adaptive and/or maladaptive nature of the response are discussed.

The effects of social defeat and other stressors on the expression of circadian rhythms.

Most biological functions display a 24 h rhythm that, in mammals, is under the control of an endogenous circadian oscillator located in the suprachiasmatic nuclei (SCN) of the hypothalamus. The circadian system provides an optimal temporal organization for physiological processes and behavior in relation to a cyclic environment imposed upon organisms by the regular alternation of day and night. In line with its function as a clock that serves to maintain a stable phase-relationship between endogenous rhythms and the light-dark cycle, the circadian oscillator appears to be well protected against unpredictable stressful stimuli. Available data do not provide convincing evidence that stress is capable of perturbing the central circadian oscillator in the SCN. However, the shape and amplitude of a rhythm is not determined exclusively by the SCN and certain stressors can strongly affect the output of the clock and the expression of the rhythms. In particular, social stress in rodents has been found to cause severe disruptions of the body temperature, heart rate and locomotor activity rhythms, especially in animals that are subject to uncontrollable stress associated with defeat and subordination. Such rhythm disturbances may be due to effects of stress on sub-oscillators that are known to exist in many tissues, which are normally under the control of the SCN, or due to other effects of stress that mask the output of the circadian system. These disturbances of peripheral rhythms represent an imbalance between normally precisely orchestrated physiological and behavioral processes that may have severe consequence for the health and well being of the organism.