Individual differences in the activity of the hypothalamus-pituitary-adrenocortical system after stressors: Use of psychogenetically selected rat lines as a … (original) (raw)
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The Role of Limbic and Hypothalamic Corticotropin-Releasing Factor in Behavioral Responses to Stress
Annals of the New York Academy of Sciences, 1993
Stress is classically defined as a nonspecific response to any demand (usually noxious) upon the body' and is accompanied by various physiological changes including activation of the pituitary-adrenal axis. This activation is dependent upon hypothalamic releasing hormones such as corticotropin-releasing factor (CRF) that regulate the secretion of adrenocorticotropic hormone (ACTH) from the pituitary. The endocrine action of ACTH in turn stimulates the release of adrenal steroid hormones which have widespread systemic effects on metabolic and immunologic variables. Because these events represent appropriate biological responses to stress,2 hypothalamo-pituitary-adrenal activation has been extensively quantified experimentally in order to infer the presence and intensity of stress in an affected organism. Later theorists emphasized the potency of psychological stimuli in inducing a stress re~ponse.~ Indeed, common physiological stressors such as exercise and hunger do not activate the pituitary-adrenal axis when they are presented in a way that eliminates the perception of fear or ~onflict.~ The salience of psychological variables suggests that there is a neurobiological substrate that interprets alerting or threatening cognitive stimuli and consequently stimulates the appropriate physiological stress response. This substrate has been hypothesized to be the brain system classically involved in the processing of emotion-the limbic system. Thus, stressors that disturb psychological homeostasis activate the pituitary-adrenal system via limbic inputs to the hypothalam~s.~,~ Although such stress-induced activation is largely dependent on the neuroendocrine action of hypothalamic CRF, the concurrent stimulation of CRF activity outside of the hypothalamo-pituitary axis (HPA) which accompanies increased emotionality suggests a direct neurotropic role for CRF in coordinating separate behavioral or autonomic responses to stress. CRF AS NEUROTRANSMITTER IN THE CENTRAL NERVOUS SYSTEM CRF immunoreactivity has been localized in the central nervous system both in the hypothalamus and in extrahypothalamic structures.' Notable are CRF-stained cells and fibers in the paraventricular nucleus (PVN) of the hypothalamus, the aCorresponding author.
Behavioural Brain Research, 2004
We have previously observed that a single exposure to immobilization (IMO), a severe stressor, caused long-term (days to weeks) desensitization of the response of the hypothalamic-pituitary-adrenal (HPA) axis to the homotypic stressor, with no changes in behavioral reactivity to novel environments. In contrast, other laboratories have reported that a single exposure to footshock induced a long-term sensitization of both HPA and behavioral responses to novel environments. To test whether these apparent discrepancies can be explained by the use of different stressors or different strains of rats, we studied in the present work the long-term effects of a single exposure to two different stressors (footshock or IMO) in two different strains of rats (Sprague-Dawley from Iffa-Credo and Wistar rats from Harlan). We found that both strains showed desensitization of the HPA response to the same (homotypic) stressor after a previous exposure to either shock or IMO. The long-term effects were higher after IMO than shock. No major changes in behavior in two novel environments (circular corridor, CC and elevated plus-maze, EPM) were observed after a single exposure to shock or IMO in neither strain, despite the fact that shocked rats showed a conditioned freezing response to the shock boxes. The present results demonstrate that long-term stress-induced desensitization of the HPA axis is a reliable phenomenon that can be observed with different stressors and strains. However, only behavioral changes related to shock-induced conditioned fear were found, which suggests that so far poorly characterized factors are determining the long-term behavioral consequences of a single exposure to stress.
Scientific Reports, 2016
Stress-induced sensitization represents a process whereby prior exposure to severe stressors leaves animals or humans in a hyper-responsive state to further stressors. Indeed, this phenomenon is assumed to be the basis of certain stress-associated pathologies, including post-traumatic stress disorder and psychosis. One biological system particularly prone to sensitization is the hypothalamic-pituitary-adrenal (HPA) axis, the prototypic stress system. It is well established that under certain conditions, prior exposure of animals to acute and chronic (triggering) stressors enhances HPA responses to novel (heterotypic) stressors on subsequent days (e.g. raised plasma ACTH and corticosterone levels). However, such changes remain somewhat controversial and thus, the present study aimed to identify the critical characteristics of the triggering and challenging stressors that affect acute stress-induced HPA cross-sensitization in adult rats. We found that HPA cross-sensitization is markedly influenced by the intensity of the triggering stressor, whereas the length of exposure mainly affects its persistence. Importantly, HPA sensitization is more evident with mild than strong challenging stressors, and it may remain unnoticed if exposure to the challenging stressor is prolonged beyond 15 min. We speculate that heterotypic HPA sensitization might have developed to optimize biologically adaptive responses to further brief stressors. Animals exposed to acute stress immediately respond by altering their behavior and physiology. Typical behavioral changes involve reduced activity and enhanced anxiety, particularly in response to relatively severe stressors 1,2. Prototypic physiological changes include the activation of components of the autonomous nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. The activation of the former mainly affects its sympathetic branch, provoking important cardiovascular changes, and the release of noradrenaline and adrenaline into the bloodstream. Stress-induced activation of the HPA axis results from a convergence of the inputs to the medial parvocellular subdivision of the hypothalamic paraventricular nucleus (mpdPVN), which contains the neurons that synthesize the corticotropin-releasing hormone (CRH) and other ACTH secretagogues (e.g. vasopressin) 3. CRH is considered the main hypothalamic stimulatory factor that controls both the synthesis and release of ACTH by corticotropin cells of the anterior pituitary. In turn, ACTH controls the synthesis and secretion of glucocorticoids from the adrenal cortex: cortisol in humans and most mammals; corticosterone in rats and mice. Stress-induced glucocorticoid release has a wide range of central and peripheral effects, including the mobilization of resources, the modulation of immune function and negative feedback 4,5. Although acute stress-induced changes are likely to be transient after exposure to mild stressors, exposure to severe and uncontrollable stressors can leave a trace that lasts for several days or weeks, and that may be reflected in neurochemical, neuroendocrine and behavioral changes 2,6,7. Indeed, the long-lasting behavioral effects of
Hormones and Behavior, 1998
The Syracuse high-and low-avoidance rats, which have been selectively bred for good (SHA/Bru) or poor (SLA/ Bru) avoidance learning in a two-way shuttle box, differ in emotionality. This experiment investigated the effect of corticotropin-releasing hormone (CRH), administered centrally (0, 0.1, 0.5, and 1.0 g), on conditioned suppression and on the hypothalamic-pituitary-adrenocortical system. Three groups of animals were used: SHA/ Bru rats conditioned at 0.21 or 0.43 mA and SLA/Bru rats conditioned at 0.21 mA. The results confirm those of previous studies which found that SLA/Bru rats show greater conditioned suppression than the SHA/Bru rats at the low shock intensity and that at 0.43 mA, the SHA/ Bru animals acquire a level of conditioning comparable to that of the SLA/Bru animals at 0.21 mA. The results show that the nonlinear behavioral effect of CRH is independent of strain and produces comparable effects in animals of both strains, but only when level of conditioning is equated. Adrenal and plasma concentrations of corticosterone increased in all three groups of animals as a direct linear function of dose of CRH. Both greater levels of conditioning and larger amounts of CRH increase the synthesis of corticosterone more in SHA/Bru animals than in the SLA/Bru animals. Thus, genetic variation, which differentiates the behavioral and endocrinological characteristics of these animals, shows that these effects of CRH can be independent of each other and suggests that some minimal level of conditioned fear is necessary for CRH to exert its anxiogenic effect.
Physiology & Behavior, 1988
rearing has long been suspected to alter hormonal and behavioral responses to stress. Two experiments were conducted to test the hypothesis that isolates are more timid or fearful than socially reared rats when exposed to novel test environments. In both, isolate response to 3 graded stressors was compared to that of socially-reared rats. In the first experiment, animals were handled, shocked or not treated prior to testing to produce three levels of conditioned fear. They were then tested on four paradigms previously shown sensitive to conditioned fear: open field activity, emergence latency, auditory startle, and latency to accept food from the experimenter. In the second experiment, rats were given a 0-, 5-or 20-rain forced swim, then sacrificed for analysis of plasma corticosterone and pituitary and hypothalamic/3-endorphin. It was found that isolates showed little evidence of enhanced behavioral timidity, although rearing effects were seen on all 4 behavioral measures. Plasma corticosterone levels increased in a graded fashion over the course of the forced swim, but there was no effect of rearing conditions. While there were no effects of rearing or stress on hypothalamic/3-endorphin, pituitary/3-endorphin content was lower in females than in males, and isolate males had lower pituitary endorphin than social males. In summary, these experiments provide no evidence that isolation rearing produces a primary, global increase in fearfulness, but identify several behavioral and hormonal differences associated with differential housing in rats.
Development of stress-induced responses in preweanling rats
Developmental Psychobiology, 1991
This study examined in postnatal Days 7, 14, and 21 male rats the effects of social isolation and social isolation with administration of brief foot shocks on the development of stress-induced behavioral and pituitary-adrenal hormone responses. Day 21 rats appeared similar to adult rats in their responses to the two test conditions. That is, exposure to either isolation or to shock increased both pituitaryadrenal hormone secretion and tail-flick latencies but only administration of shock potentiated freezing and ultrasonic vocalizations. Younger rats differed from Day 21 rats in their responses to the two test conditions. In both tests, Day 7 rats produced the highest number of ultrasounds, which may be due to a significant decrease in body temperature. In contrast, in Day 14 pups, exposure to shock significantly reduced isolation-induced ultrasonic vocalizations. Additional age-dependent differences were found in the analgesic responses of Days 7 and 14 rats. Day 7 rats exposed to stress became consistently hyperalgesic whereas Day 14 rats showed only a short-lasting analgesic response. Although in Days 7 and 14 rats exposure to the two stress conditions produced significant elevations in pituitary-adrenal hormone concentrations, plasma levels were lower than those measured in Day 21 rats. To summarize, preweanling rats exhibit varied age-dependent responses when exposed to different stress environments In adulthood, exposure to a stressor or a threat results in the rapid expression of defensive patterns of behavior and activation of the hypothalamic-pituitaryadrenal (HPA) system. Importantly, defensive behavioral and endocrine responses are not stereotypic in expression but are increased or decreased depending on the intensity of the stressor. For example, in adult Norway rats, shock-induced defensive freezing and crouching postures (Blanchard & Blanchard, 1969; Fanselow & Bolles, 1979), which are behavioral indices of fear in animals (Ratner, 1967) are reported to occur more frequently as the intensity of electric foot shock increases. Adrenal corticosterone secretion also increases positively as a function of stressor intensity (Coover, Sutton, Welle, & Hart, 1978). By having the capacity Reprint requests should be sent to Dr.
1997
The presence of noradrenergic terminals that synapse on corticotropinreleasing hormone (CRH) cells in the paraventricular nucleus (PVN) of the hypothalamus suggests a relationship between hypothalamic-pituitaryadrenocortical (HPA) function and central noradrenergic activity (1 ). Norepinephrine (NE) is thought to be a potent stimulator of CRH neurons. Surgical or chemical transection of the ascending ventral noradrenergic bundle markedly decreases tissue and extracellular basal concentrations of NE, immunoreactive CRH-41, and CRH messenger RNA (mRNA) in the ipsilateral PVN (2, 3). Coronal hemisection of the brain stem between the locus ceruleus and the rostra1 portion of the medulla oblongata also markedly decreases release of NE and expression of CRH mRNA in the PVN in rats exposed to immobilization stress (2).