Chronic restraint or variable stresses differently affect the behavior, corticosterone secretion and body weight in rats

Organisms are constantly subjected to stressful stimuli that affect numerous physiological processes and activate the hypothalamo-pituitary-adrenal (HPA) axis, increasing the release of glucocorticoids. Exposure to chronic stress is known to alter basic mechanisms of the stress response. The purpose of the present study was to compare the effect of two different stress paradigms (chronic restraint or variable stress) on behavioral and corticosterone release to a subsequent exposure to stressors. Considering that the HPA axis might respond differently when it is challenged with a novel or a familiar stressor we investigated the changes in the corticosterone levels following the exposure to two stressors: restraint (familiar stress) or forced novelty (novel stress). The changes in the behavioral response were evaluated by measuring the locomotor response to a novel environment. In addition, we examined changes in body, adrenals, and thymus weights in response to the chronic paradigms. Our results showed that exposure to chronic variable stress increased basal plasma corticosterone levels and that both, chronic restraint and variable stresses, promote higher corticosterone levels in response to a novel environment, but not to a challenge restraint stress, as compared to the control (non-stressed) group. Exposure to chronic restraint leads to increased novelty-induced locomotor activity. Furthermore, only the exposure to variable stress reduced body weights. In conclusion, the present results provide additional evidence on how chronic stress affects the organism physiology and point to the importance of the chronic paradigm and challenge stress on the behavioral and hormonal adaptations induced by chronic stress.     

Behavioral, neuroendocrine, and immunological outcomes of escapable or inescapable shocks.

The present study was designed to evaluate the effects of repeated exposure to escapable or inescapable shocks on subsequent behavior in an activity cage, and on the reactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the immune system. We also studied the possible influence of behavioral factors on the behavioral and physiological impact of stress. Although exposure to different stressful situations pointed out marked differential effects in subsequent behavior, it failed to elicit differences in the neuroendocrine and immunological parameters studied. However, interesting results were found in analyzing the influence of behavioral factors. The degree of control exerted over the shock was inversely related to ACTH and corticosterone levels. In addition, individual differences in the exploratory activity to novelty were correlated with poststress lymphoproliferation and antibody formation. These data indicate that the behavioral and physiological outcomes of stress depend on the interrelations between environmental and individual factors (including both preexisting individual differences and the coping responses during stress).     

Divergent stress-induced neuroendocrine and behavioral responses prior to puberty

Following an acute stressor, pre-adolescent rats exhibit a protracted hormonal response compared to adults, while after repeated exposure to the same stressor (i.e., homotypic stress) prepubertal males fail to habituate like adults. Though the neurobehavioral implications of these changes are unknown, studying pubertal shifts in stress reactivity may help elucidate the mechanisms that underlie the increase in stress-related psychological and physiological disorders often observed during adolescence. Here, we investigated hormonal, behavioral, and neural responses of prepubertal (30d) and adult (77d) male rats before, during, or after acute stress (restraint), homotypic stress (repeated restraint) or heterotypic stress (repeated cold exposure followed by restraint). We found that prepubertal males exhibit prolonged corticosterone responses following acute and heterotypic stress, and higher adrenocorticotropic hormone and corticosterone responses after homotypic stress, compared to adults. Despite these significant age-dependent changes in hormonal responsiveness, we found that struggling behavior during restraint was similar at both ages, such that both prepubertal and adult animals exposed to homotypic stress struggled less than animals exposed to either acute or heterotypic stress. Across these different stress paradigms, we found greater neural activation, as indexed by FOS immunostaining, in the prepubertal compared to adult paraventricular nucleus of the hypothalamus, a nucleus integral for initiating the hormonal stress response. Interestingly, however, we did not find any influence of pubertal development on stress-induced activation of the posterior paraventricular thalamic nucleus, a brain region involved in experience-dependent changes in stress reactivity. Collectively, our data indicate that prepubertal and adult males display divergent hormonal, behavioral, and neural responses following a variety of stressful experiences, as well as a distinct dissociation between hormonal and behavioral reactivity in prepubertal males under homotypic conditions.     

Heart rate dynamics and behavioral responses during acute emotional challenge in corticotropin-releasing factor receptor 1-deficient and corticotropin-releasing factor-overexpressing mice

The role of corticotropin-releasing factor in autonomic regulation of heart rate, heart rate variability and behavior responses was investigated in two genetic mouse models: corticotropin-releasing factor receptor 1-deficient mice, and corticotropin-releasing factor-transgenic mice overexpressing corticotropin-releasing factor. Heart rate was recorded by radio-telemetry during novelty exposure and auditory fear conditioning. Locomotor activity and freezing served as behavioral indices. Locomotor activity and heart rate were invariably increased in response to novelty exposure in both corticotropin-releasing factor receptor 1-deficient mice and littermate wild-type controls. The heart rate responses during retention of conditioned auditory fear and the exponential relationship between heart rate and heart rate variability were unaffected by genotype. Moreover, conditioned fear responses inferred from multiple behavioral measures including freezing did not differ between corticotropin-releasing factor receptor 1-deficient and corticotropin-releasing factor receptor 1 wild-type control mice. Corticotropin-releasing factor-transgenic mice exhibited markedly reduced locomotor activity during novelty exposure when compared with littermate wild-type controls. Baseline and novelty-driven heart rate was slightly elevated in corticotropin-releasing factor-transgenic mice, whereas the novelty-induced increase of heart rate was not different between genotypes. In contrast, corticotropin-releasing factor-transgenic mice did not display a heart rate response indicative of conditioned auditory fear. It is concluded that corticotropin-releasing factor receptor 1-deficiency does not affect heart rate adjustment and behavioral responses to acute fearful stimuli. The resiliency of behavioral and cardiovascular patterns elevation argues against the involvement of corticotropin-releasing factor receptor 1 in acute emotional regulation on these two functional levels despite an absent corticosterone elevation in corticotropin-releasing factor receptor 1-deficient mice. It is hypothesized that the lack of a conditioned heart rate response in corticotropin-releasing factor-transgenic mice is attributable to an impairment of cognitive function. The results are compared with those of corticotropin-releasing factor receptor 2-deficient mice, and the role of the corticotropin-releasing factor system in cardiovascular regulation is discussed.     

Corticosterone and prolactin responses to predictable and unpredictable novelty stress in rats

Prolactin along with corticosterone is a stress responsive hormone. The present study examined the effect of predictable and unpredictable psychological stress on corticosterone and prolactin secretion. Repeated unpredictable exposure to the novelty cage produced a more substantial increase in the level of corticosterone than predictable exposure to the same novelty apparatus. In contrast, predictable novelty stress induced a more substantial elevation in prolactin levels than unpredictable stress. Furthermore, it was observed that both corticosterone and prolactin returned to control levels 30 minutes after the fifth exposure to the novelty cage. It was concluded that the pattern of exposure to novelty is an important paradigm which effects the magnitude of hormonal responding. An important relationship between corticosterone release and prolactin secretion is also indicated.     

Immobilization stress rapidly modulates BDNF mRNA expression in the hypothalamus of adult male rats

Considerable evidence has focused on the interaction between endogenous opioid peptides and the dopaminergic mesocorticolimbic system in behavioral responses to stress. Recently, it has been proposed that the CNS synthesizes and secretes neuropeptides that act as part of a homeostatic system to attenuate the effects of morphine or endogenous opioid peptides. Among these antiopioids, neuropeptide FF (NPFF) is particularly interesting since both NPFF immunoreactive-like terminals and NPFF binding sites are located in the vicinity of the dopaminergic cell bodies within the ventral tegmental area (VTA) suggesting an interaction at this level. The purpose of the present study was to evaluate the respective implication of opioid and antiopioid peptides at the level of the VTA in the locomotor response to novelty in rats. The results indicate that s.c. naloxone pretreatment, an opiate receptor antagonist, reduced locomotor activity in rats placed in a novel environment without having any effect in a familiar environment. This effect takes place in the VTA since intra-VTA administration of naloxone methobromide diminished similarly and dose-dependently the motor response to novelty. This effect is mainly dependent on opioid peptides released at VTA level since local injections of thiorphan, an inhibitor of enkephalin degradation, strongly increased locomotor response to novelty and this effect is completely prevented by the co-administration of naloxone methobromide. When injected in the VTA, NPFF is acting as an antiopioid compound, i.e. it reduces the locomotor activity triggered by exposure to novelty to the level recorded in a familiar environment. Moreover, NPFF decreased dose-dependently the potentiation of novelty-induced locomotor response produced by VTA injection of thiorphan. Taken together, these results suggest that NPFF neurons may participate at the level of the VTA to a homeostatic regulating process counteracting opioid effects induced by a mild stress such as novelty.     

Effects of prolonged exposure to context following contextual fear conditioning on synaptic properties in rat hippocampal slices

Acute stressful events enhance plasma corticosterone release and profoundly affect synaptic functions, which are involved in the development of stress-related cognitive and mental disorders. However, how exposure to stressful context immediately after stress further modulates the physiological responses is not fully understood. Here, we found that acute stress inhibited paired-pulse facilitation in hippocampal slices of Wistar rats which were subjected to contextual fear conditioning. But such inhibition was reversed by subsequent prolonged exposure to foot-shock context or returning to home cage for 1 h. Interestingly, foot-shock stress-facilitated LTD induced by low frequency stimulation (LFS, 900 pulses at 1 Hz) was maintained by subsequent exposure to foot-shock context but was reversed by returning to home cage environment. Moreover, plasma corticosterone level was still kept higher in rats exposed to foot-shock context but not to home cage. Findings suggest that remaining in stressful environment immediately after stress maintains acute stress-facilitated LTD and higher level of neuroendocrine response. Our results also contribute to further understanding the critical role of timely intervention in mediating stress-related aversive changes in human.     

Social environment determines the long-term effects of social defeat

A single social defeat by a dominant conspecific induces long-term changes in several physiological and behavioral parameters in rats. These changes may represent an increased vulnerability to subsequent stress and stress-related pathology. Environmental factors, in particular possibilities for social interactions, could modulate these effects. Therefore, we assessed the influence of social environment on susceptibility for the long-term effects of social defeat. Socially housed males of an unselected strain of wild-type rats were equipped with radio-telemetry transmitters that recorded heart rate, temperature and activity. They were individually subjected to defeat and subsequently either housed alone or returned to their group. Behavioral and physiological responses to various novelty stressors were determined during a three-week period after the social defeat. Furthermore, changes in baseline behavior and physiology following defeat were studied in the rat's homecage. The results show a complex interaction between defeat and housing conditions. Depending on the parameters measured, effects were caused by both isolation alone, defeat alone or a combination of both defeat and isolation. Individual housing alone caused a characteristic hyperactive response to novelty stress. Though defeat did not affect behavioral responses, it amplified the physiological response to novelty and social housing did not attenuate this effect. However, social housing did reduce the effects of defeat on heart rate, temperature and activity in the home cage and completely prevented defeat-induced weight loss. Together these results indicate that social housing may indeed positively affect the animal's capacity to cope with stressors.     

Influence of perinatal malnutrition on adult physiological and behavioral reactivity in rats

A series of experiments examined the behavioral and pituitary-adrenal response to novelty of perinatally malnourished rats tested as adults after nutritional rehabilitation begun at weaning. Neither the behavioral measures of ambulation, rearing and defecation, nor the plasma corticosterone response to a brief exposure to an open field differentiated the previously malnourished subjects from controls. Similar to controls, previously malnourished subjects were also capable of displaying a graded corticoid elevation to environments increasingly different from the home cage. However, exploratory behavior, as measured by head-dip frequency and duration in the hole-board, was reduced in the previously malnourished rats. Although latency and amount of fluid consumed in a novel environment did not differ, previously malnourished rats were unable to use the cues associated with a consummatory behavior to modulate the pituitary-adrenal response to novelty. Thus, perinatal malnutrition does not influence either the behavioral or physiological activational response to novel stimulation but appears to alter the ability of the animal to use a consummatory behavior to modulate this response.     

Habituation to the test cage influences amphetamine-induced locomotion and Fos expression and increases FosB/DeltaFosB-like immunoreactivity in mice

Pre-exposure to the testing cage (habituation or familiarization) is a common procedure aimed at reducing the interference of novelty-induced arousal and drug-independent individual differences on neural and behavioral measures. However, recent results suggest that this procedure might exert a major influence on the effects of addictive drugs. The present experiments tested the effects of repeated exposure to a test cage (1 h daily for four consecutive days) on amphetamine-induced locomotion and Fos expression as well as on FosB/DeltaFosB-like immunoreactivity in mice of the C57BL/6J and DBA/2J inbred strains that differ for the response to amphetamine, stress and novelty. Daily experiences with the test cage increased FosB/DeltaFosB-like immunoreactivity in the medial-prefrontal cortex of both strains of mice and in the caudate of mice of the C57 strain, as reported for repeated stress in the rat. Moreover, previous habituation to the test cage reduced the locomotor response to a low dose of amphetamine only in DBA mice while it reduced amphetamine-induced Fos expression in medial-prefrontal cortex, dorsal caudate and the accumbens shell of mice of the C57 strain. These results demonstrate indexes of stress-like plasticity in the brains of mice exposed to a procedure of familiarization to the testing environment. Moreover, they suggest that the procedure of daily familiarization influences the pattern of brain Fos expression induced by amphetamine. Finally, they indicate complex interactions between experience with the testing environment, genotype and drug.     

Olfactory bulbectomy induces rapid and stable changes in basal and stress-induced locomotor activity,heart rate and body temperature responses in the home cage

Background: Olfactory bulbectomy (OBX) in rats causes several behavioral and neurochemical changes. However, the extent and onset of physiological and behavioral changes induced after bulbectomy have been little examined. Methods: Male Sprague–Dawley rats received telemetric implants. Before and immediately after OBX surgery, basal and stress-induced heart rate, body temperature, and locomotor activity were measured in the home cage in sham (n=9) and OBX animals (n=11). Stress was induced using novel cage stress or witness stress. Results: Bulbectomized animals differed physiologically and behaviorally from shams. Nocturnally, OBX animals were significantly more active compared with shams, had a higher core body temperature and displayed a decreased heart rate variability. During the light period, OBX animals had a significantly lower basal heart rate and a reduced heart rate variability. These effects became apparent 2–3 days after OBX surgery, and were stable over time. After witness stress, OBX animals showed smaller autonomic (body temperature and heart rate) responses compared with shams, but showed no difference in locomotor responses. In contrast, novel cage stress led to increased locomotor responses in OBX rats compared with sham rats, while no differences were found in autonomic responses. Conclusion: Removal of the olfactory bulbs results in rapid, stable and persistent changes in basal locomotor activity, body temperature, heart rate and heart rate variability. Although the sleep–wake cycle of these parameters is not altered, increases in circadian amplitude are apparent within 3 days after surgery. This indicates that physiological changes in the OBX rat are the immediate result of olfactory bulb removal. Further, stress responsivity in OBX rats depends on stressor intensity. Bulbectomized rats display smaller temperature and heart rate responses to less intense witness stress compared with sham rats. Increased locomotor responses to more intense novel cage stress are present in the home cage as well as the open field. The present study shows that olfactory bulbectomy has rapid and persistent influence on basal and stress-induced physiological parameters.     

Behavioral sensitivity to corticosterone in juveniles of the wall lizard, Podarcis muralis

Reptiles exposed to stressful conditions respond with increases in plasma levels of corticosterone (CORT). The outcome of such hormonal fluctuations can affect the organism's physiology and behavior; however, relatively few studies in reptiles have progressed past the effects of stress on the plasma levels of CORT. The purpose of this study was to investigate the effects of CORT on lizard behavior. We focused on activity and thermoregulation of juveniles of the wall lizard, Podarcis muralis. Juveniles with experimentally elevated plasma CORT concentrations showed a higher moving rate and spent a greater amount of time moving. They also spent more time being involved in attempts to escape from a terrarium. This enhanced locomotor activity was associated with significant changes in thermoregulatory behavior, as CORT-increased individuals had reduced thermoregulatory activity than the controls. The same pattern of results was obtained in nature and under laboratory conditions. Thus, CORT levels appear to mediate an important trade-off between locomotor activity and thermoregulation. To our knowledge, this is the first time that the effect of CORT on lizard thermoregulation has been examined.     

High and low responders to novelty: effects of a catecholamine synthesis inhibitor on novelty-induced changes in behaviour and release of accumbal dopamine.

The purpose of the present study was two-fold: (i) to investigate to what extent novelty, i.e. a novel cage with slightly larger dimensions than the home cage and lacking the floor covering that was originally present, produced behavioural effects in high responders to novelty and low responders to novelty that could be correlated with the extracellular amount of accumbal dopamine, using the microdialysis technique, and (ii) to establish the ability of the catecholamine synthesis inhibitor alpha-methyl-p-tyrosine to inhibit the novelty-induced responses in high and low responders. The difference in the behavioural response to novelty between the high and low responders was limited to walking, which lasted significantly longer in high responders than in low responders. The novelty-induced increase in extracellular concentration of accumbal dopamine was significantly greater in high responders than in low responders; moreover, the shape of the growth curves differed between high and low responders. The behavioural changes did not correlate with the neurochemical effects, which outlasted the duration of the novelty-induced behavioural arousal. It is hypothesized that this long-lasting increase in accumbal dopamine produces "adaptive changes" that help and/or allow the animal to incorporate knowledge about the condition that it experienced. When the nucleus accumbens was perfused with alpha-methyl-p-tyrosine for a period of 40 min, given at the same time as the transfer of the rat to the novel cage, it reduced the novelty-induced increase in walking in the high responders, but did not alter the novelty-induced behaviour of low responders. Finally, alpha-methyl-p-tyrosine reduced the novelty-induced increase in the release of accumbal dopamine in high responders, but enhanced it in low responders. The present neurochemical data are discussed in view of the outcome of earlier reported pharmacobehavioural studies on the neurochemical state of the nucleus accumbens of non-challenged versus challenged high and low responders. It is hypothesized that, in the high responder, exposure to novelty enhances the release of accumbal dopamine from reserpine-resistant, alpha-methyl-p-tyrosine-sensitive pools that are under the stimulatory control of beta-adrenergic receptors in the nucleus accumbens, and that, in the low responder, exposure to novelty enhances the release of accumbal dopamine from reserpine-sensitive, alpha-methyl-p-tyrosine-resistant pools that are under the inhibitory control of alpha-adrenergic receptors in the nucleus accumbens.     

Behavioral indicators of stress-coping style in rainbow trout: Do males and females react differently to novelty?

It is becoming increasingly clear that individual differences in the behavioral response to stressful situations are associated with distinct physiological profiles, and stress coping characteristics are of fundamental importance to fitness and life history. Teleost fishes display considerable variation in reproductive strategy, but sex differences in stress-coping style have not been described previously in fish. Prior to sexual maturation, the glucocorticoid response to stress is not affected by sex in salmonid fish. Nevertheless, behavior in novel and stressful situations differed between immature male and female rainbow trout (Oncorhynchus mykiss). When tested 1 week following transport to a new rearing facility, females resumed feeding after transfer to social isolation quicker than males. The locomotor response to acute confinement stress also varied between sexes, with females settling down and ceasing to move in a panic-like manner quicker than males. There was a strong correlation between behavior in the two test situations: individuals that readily resumed feeding behavior in a new environment also moved less in the acute stress test. Thus, the time to resume feeding after a stressful experience is a precise indicator of stress-coping style in salmonid fish, which is likely to reflect the dynamics of neuroendocrine stress responses. Furthermore, these observations could reflect a sex difference in the response to novel and stressful situations, which occur even in the absence of differences in glucocorticoid responsiveness.     

Reactivity of the Hypophyseal-Adrenocortical System to Stress in Rats with Active and Passive Behavioral Strategies

Rats with active (KHA) and passive (KLA) behavioral strategies showed no strain-related differences in basal corticosterone levels or in changes in corticosterone levels after exposure to mildly stressful stimuli. Only severe immobilization stress produced significant interstrain differences in the reactivity of the hypophyseal-adrenocortical system, as evidenced by the greater increase in blood corticosterone in KHA rats 30 min after stressing. The hormonal stress response in KHA rats was prolonged, as the elevated blood corticosterone level in these animals persisted longer than in KLA rats. The data provide evidence not only that the hypophyseal-adrenocortical systems have different sensitivities to severe stresses in these strains, but also that active and passive animals have different rates of inactivation of the stress reaction.     

Behavioral and physiological responses to stress are affected by high-fat feeding in male rats.

Interactions between monoaminergic neurochemistry and macronutrient intake have been frequently shown. Because monoaminergic systems in the brain are also closely involved in behavioral and physiological stress responses it can be hypothesized that differences in the macronutrient composition of diets are reflected in these responses. The present studies, therefore, were designed to assess the consequences of a change in dietary macronutrient composition on a variety of physiological and behavioral responses (both acute and long-term) to a number of stressors. The effect of chronic high-fat (HF; 61% kcal from fat) feeding on the stress responses was compared with controls receiving regular high-carbohydrate (HC; 63% kcal from carbohydrates) laboratory chow. Rats were kept on this diet for at least 2 months before they were exposed to either psychological (social defeat) or physiological (lipopolysaccharide, LPS, administration) stress. At baseline, chronic HF feeding caused a slight, but significantly reduction in body temperature relative to that observed in HC-fed rats. Following social defeat or LPS injection, HF feeding caused a faster recovery of the body temperature increase relative to animals on the HC diet. Stress-induced suppression of home cage locomotor activity and body weight gain were also reduced by HF feeding. The serotonergic 5-HT(1a) receptor hyposensitivity that was observed in HC-fed rats 2 weeks after stress was absent in the HF regimen. Although the present results cannot be readily interpreted as showing purely beneficial effects of high-fat diets on stress responsivity, the findings in the present study do encourage further investigation of possible ameliorating effects of high-fat diets on aspects of the behavioral and physiological response stress.     

The Effects of Peripheral Chemosympathectomy and Adrenalectomy Upon Blood Pressure Responses of the Rat to Footshock Under Varying Conditions: Evidence for Behavioral Effects on Patterning of Sympathetic Nervous System Responses

A significant decrease in blood pressure is observed after shock-induced fighting in intact rats. In rats treated with intravenous 6-hydroxydopamine, a drug that selectively destroys peripheral sympathetic nerve endings when given by this route, this blood pressure response is reversed to a significant increase. In contrast, adrenalectomy converts a slight increase in blood pressure after intact rats are shocked alone in the cage into a significant decrease. These alterations in blood pressure response suggest that the sympathetic response to a stressful stimulus is not an all or none response, but, rather, consists of a patterned activation depending upon the behavioral response available. The current physiological findings are consistent with neuroendocrine research in which coping behavior is found associated with a predominant norepinephrine release by the sympathetic nervous system, and stress without available coping responses is associated with release also of epinephrine.     

Early impact of a fat-enriched diet on behavioral responses of male and female rats

Prolonged high-fat diets have been shown to affect an organism's stress responsiveness at the neuroendocrine level. In the present study, the authors used a 7-day protocol of fat administration in adult rats of both sexes to investigate the early behavioral impact of a moderately fat (20%) diet, often used by Western societies, on rats' reaction to acute stress and novelty. Their results show that this diet can reduce the rats' active behavioral responses to subsequent stressors and influence their corticosterone secretion. Fat-fed male rats adopted a less active behavior to cope with forced swimming stress, whereas their exploratory behavior in the open field environment was rather increased compared with chow-fed males. Fat-fed female rats exhibited a less active behavioral response to both stress paradigms compared with their chow-fed counterparts. Fat diet abolished facilitation in corticosterone secretion following a subsequent stressor in both sexes. However, only in males did fat diet exaggerate corticosterone response to novelty, irrespective of the previous stress history of the rat. These data indicate that a short-term metabolic stress can modify the rats' stress coping strategy in interaction with the gender.     

Involvement of corticosterone in cardiovascular responses to an open-field novelty stressor in freely moving rats

The aim of the present study was to investigate the modulatory action of different concentrations of circulating corticosterone occupying either predominantly mineralocorticoid receptors (MR) or both MR and glucocorticoid receptors (GR) in control of cardiovascular responses to a novelty stressor. Six groups of rats were instrumented with radiotelemetry transmitters: sham-operated controls, adrenalectomised (ADX) controls, ADX with chronic implantation of a 20-mg corticosterone pellet, ADX with chronic implantation of a 100-mg corticosterone pellet, ADX receiving acute bolus injection of 0.25 mg/kg of corticosterone, and ADX with both implantation of a 20-mg corticosterone pellet and bolus treatment. Exposure to the novelty of an open field caused an increase in blood pressure, heart rate, body temperature and exploratory locomotor activity. The pressor response was dose-dependently increased in ADX rats implanted with a corticosterone pellet. Bolus injection of corticosterone at 10 min prior to novelty had no effect. The tachycardia was reduced in ADX rats compared to sham-operated controls, and this effect was restored by implantation of a 20-mg, but not 100-mg, corticosterone pellet. Bolus injection of corticosterone facilitated the return of heart rate towards baseline levels. The increase in body temperature was reduced in ADX rats, a deficit that was normalised by implantation of either corticosterone dose but not by acute bolus treatment. Locomotor activity was not different between the groups except for a slightly more rapid decline of locomotor activity in both groups treated with a bolus injection of corticosterone. These data show an important role of putative brain MR in maintaining adequate cardiovascular and behavioural responsiveness to a mild psychological stressor, while additional acute or chronic occupation of GR has further differential and sometimes opposing effects.     

Corticotropin releasing factor (CRF) and age-related differences in behavior of mice

Aged rodents demonstrate a difference in response to the stress of a novel environment compared to young rodents. Corticotropin releasing factor (CRF) is involved in both the hormonal and motor response to stressful stimuli. The contribution of CRF to age-related differences in behavior was investigated by assessing the response to intracerebroventricular (ICV) injection of CRF in old (27 month) and mature (10 month) C57BL male mice. Open field behavior was also observed. Old mice demonstrated less locomotion and less rearing than mature mice (p less than 0.01). ICV injection of CRF increased corticosterone compared to vehicle control (p less than 0.001) without an age-related difference. CRF decreased food consumption (p less than 0.001) in all animals but had no effect on locomotion (p greater than 0.3); no significant age-related differences were observed. These findings suggest that age-related differences in response to environmental novelty are not due to increased release of CRF.