Bhatnagar S, Dallman M. Neuroanatomical basis for facilitation of hypothalamic-pituitary-adrenal responses to a novel stressor after chronic stress. Neuroscience 84: 1025-1039

Department of Physiology, University of California at San Francisco, 94143-0444, USA.
Neuroscience (Impact Factor: 3.36). 07/1998; 84(4):1025-39. DOI: 10.1016/S0306-4522(97)00577-0
Source: PubMed


Animals exposed to chronic stress exhibit normal or enhanced hypothalamic-pituitary adrenal responses to novel, acute stimuli despite the inhibitory endogenous corticosteroid response to the chronic stressor. Prior stress is thought to induce a central facilitatory trace that, upon exposure to a novel stimulus, balances or overcomes the inhibitory effects of corticosterone. The neuroanatomical basis for this facilitation of hypothalamic pituitary adrenal responses is unknown. In this study, we first show increased adrenocorticotropin and corticosterone responses to the novel stressor of restraint in rats exposed to intermittent cold for seven days. We then compared numbers of Fos-immunoreactive cells in 26 sites in control and chronically stressed rats at various times after onset of a 30 min restraint. At 60 min, density of Fos-stained cells was significantly higher in chronically stressed than in control rats in the parabrachial/Kölliker-Fuse area, posterior paraventricular thalamus, central, basolateral and basomedial nuclei of the amygdala and parvocellular paraventricular hypothalamus. The posterior paraventricular nucleus of the thalamus receives projections from the parabrachial nucleus and projects heavily to the differentially stained subnuclei of the amygdala, which in turn project to the parvocellular paraventricular nucleus of the hypothalamus. We propose that increased activity in the parabrachial-posterior paraventricular thalamus-amygdala-parvocellular paraventricular hypothalamus underlies facilitation of the hypothalamic pituitary-adrenal axis to novel stress in chronically stressed rats. We confirmed part of this proposal by showing that lesions of the posterior paraventricular nucleus of the thalamus increase adrenocorticotropin responses to restraint only in previously chronically stressed animals. This potential circuit provides a basis for further examination of the functional roles of these regions in stress-induced facilitation of hypothalamic pituitary-adrenal activity.

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    • "The predictability of chronic restraint stress administration was decreased in order to increase the effectiveness of the stressor on altering spatial performance, because repeated exposure to the same stressor leads to habituation of the HPA axis [77]. Habituation to a stressor depends on an organism's ability to recognize the familiarity of stressor and if an animal encounters a novel stressor then the response of the HPA axis can be enhanced [3]. Indeed, some studies have shown that the physical context in which a repeated stressor is administered affects subsequent HPA responses to the stressor [26]. "
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    ABSTRACT: Chronic restraint stress alters hippocampal-dependent spatial learning and memory in a sex-dependent manner, impairing spatial performance in male rats and leaving intact or facilitating performance in female rats. Moreover, these stress-induced spatial memory deficits improve following post-stress recovery in males. The current study examined whether restraint administered in an unpredictable manner would eliminate these sex differences and impact a post-stress period on spatial ability and limbic glutamic acid decarboxylase (GAD65) expression. Male (n=30) and female (n=30) adult Sprague-Dawley rats were assigned to non-stressed control (Con), chronic stress (Str-Imm), or chronic stress given a post-stress recovery period (Str-Rec). Stressed rats were unpredictably restrained for 21 days using daily non-repeated combinations of physical context, duration, and time of day. Then, all rats were tested on the radial arm water maze (RAWM) for two days and given one retention trial on the third day, with brains removed 30minutes later to assess GAD65 mRNA. In Str-Imm males, deficits occurred on day 1 of RAWM acquisition, an impairment that was not evident in the Str-Rec group. In contrast, females did not show significant outcomes following chronic stress or post-stress recovery. In males, amygdalar GAD65 expression negatively correlated with RAWM performance on day 1. In females, hippocampal CA1 GAD65 positively correlated with RAWM performance on day 1. These results demonstrate that GABAergic function may contribute to the sex differences observed following chronic stress. Furthermore, unpredictable restraint and a recovery period failed to eliminate the sex differences on spatial learning and memory. Copyright © 2015. Published by Elsevier B.V.
    Behavioural Brain Research 01/2015; 282. DOI:10.1016/j.bbr.2014.12.051 · 3.03 Impact Factor
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    • "Experiments that investigated neuronal activation of the PVT have consistently shown that this brain region is recruited during periods of arousal or by stress (Peng et al., 1995; Bhatnagar and Dallman, 1998; Novak and Nunez, 1998; Bubser and Deutch, 1999; Novak et al., 2000b; Otake et al., 2002). The PVT has also been implicated in the regulation of food intake and hypothalamic-pituitary-adrenal activity in response to chronic stress, food consumption, and energy balance (Bhatnagar and Dallman, 1998, 1999; Jaferi et al., 2003). "
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    ABSTRACT: A major challenge for the successful treatment of drug addiction is the long-lasting susceptibility to relapse and multiple processes that have been implicated in the compulsion to resume drug intake during abstinence. Recently, the orexin/hypocretin (Orx/Hcrt) system has been shown to play a role in drug-seeking behavior. The Orx/Hcrt system regulates a wide range of physiological processes, including feeding, energy metabolism, and arousal. It has also been shown to be recruited by drugs of abuse. Orx/Hcrt neurons are predominantly located in the lateral hypothalamus that projects to the paraventricular nucleus of the thalamus (PVT), a region that has been identified as a "way-station" that processes information and then modulates the mesolimbic reward and extrahypothalamic stress systems. Although not thought to be part of the "drug addiction circuitry", recent evidence indicates that the PVT is involved in the modulation of reward function in general and drug-directed behavior in particular. Evidence indicates a role for Orx/Hcrt transmission in the PVT in the modulation of reward function in general and drug-directed behavior in particular. One hypothesis is that following repeated drug exposure, the Orx/Hcrt system acquires a preferential role in mediating the effects of drugs vs. natural rewards. The present review discusses recent findings that suggest maladaptive recruitment of the PVT by drugs of abuse, specifically Orx/Hcrt-PVT neurotransmission.
    Frontiers in Behavioral Neuroscience 04/2014; 8:117. DOI:10.3389/fnbeh.2014.00117 · 3.27 Impact Factor
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    • "Other types of challenges, such as restraint stress, may also be used to induce stressful conditions in zebrafish and elicit an anxiety-like or depression-like response (Piato et al. 2011b). Zebrafish exposed to CUS display increased anxiety, impaired learning, increased levels of corticotropin releasing factor (CRF), and lower GR levels (Piato et al. 2011a), paralleling rodent behavioral (Monleon et al. 1995; Willner 2005) and neurochemical depression-like phenotypes (Schweizer et al. 2009; Bhatnagar and Dallman 1998). "
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    ABSTRACT: Depression is a serious psychiatric condition affecting millions of patients worldwide. Unipolar depression is characterized by low mood, anhedonia, social withdrawal and other severely debilitating psychiatric symptoms. Bipolar disorder manifests in alternating depressed mood and 'hyperactive' manic/hypomanic states. Animal experimental models are an invaluable tool for research into the pathogenesis of bipolar/unipolar depression, and for the development of potential treatments. Due to their high throughput value, genetic tractability, low cost and quick reproductive cycle, zebrafish (Danio rerio) have emerged as a promising new model species for studying brain disorders. Here, we discuss the developing utility of zebrafish for studying depression disorders, and outline future areas of research in this field. We argue that zebrafish represent a useful model organism for studying depression and its behavioral, genetic and physiological mechanisms, as well as for anti-depressant drug discovery.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 03/2014; 55. DOI:10.1016/j.pnpbp.2014.03.003 · 3.69 Impact Factor
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