Preface

Stress is a phenomenon being all around us, but seemingly being too well known and too little understood at the same time, despite the fact that the field has advanced enormously over recent years. We have learned that stress can shape various types of behaviour in the individual long after exposure to the stressor itself has terminated. Exposure to a stressful stimulus during the perinatal period, for example, can have long-term consequences over weeks and months, well into adulthood. This is...

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Compared with controls (sham-operated animals), suppression of corticosterone by adrenalectomy (ADX) decreases responding for cocaine during a self-administration task. The effects of ADX are reversed dose-dependently by corticosterone replacement (corticosterone added to the drinking solution of the animals ADX + Cort). The response to cocaine is fully restored when animals receive a replacement treatment reproducing stress levels of corticosterone. Modified from Deroche et al....

Altered regulation of CRF pathways CRFBP transgenic mice

As discussed above, CRF-BP binds CRF and urocortin 1 with an affinity equal to or greater than the CRF, receptor (Behan et al., 1989 Potter et al., 1991 Cortright et al., 1995), leading to the postulate that this molecule may regulate CRF actions in vivo by clearance of CRF and reduced availability for binding to CRF receptors. However, while the affinity of CRF for CRF, receptors and CRF-BP is similar, CRF interacts with CRF-BP with slower kinetics. Thus, an interaction between CRF and...

B9

Daily abdominal temperature (mean s.d.) of unrestrained rabbits for the first seven days after implantation of osmotic pumps (day 1) continuously infusing saline (open symbols, n 5) or a Gram-negative pyrogen, lipopoly-saccharide (0.2 ng 1 kg1 min ', closed symbols, w 5) sub-cutaneously. Arrow indicates time of implantation. Daily temperatures are averages of 5-min values for each rabbit. Dotted line represents mean daily body temperature of rabbits implanted with loggers only....

Contents Part

Environmental and Genetic Factors Influencing Stress Reactivity 1.1. Hypothalamic- pituitary adrenal axis in postnatal life D.M. V zquez and S. Levine (Ann Arbor, MI and Davis, CA, USA) 3 1.2. Early-life environmental manipulations in rodents and primates potential animal models in depression research C.R. Pryce, D. R edi-Bettschen, A.C. Dettling and J. Feldon 1.3. Gene targeted animals with alterations in corticotropin pathways new insights S.C. Coste, S.E. Murray and M.P....

CRF pathways

Corticotropin-releasing factor (CRF) is well known for its requisite role in initiating the pituitary-adrenal response to stress. Hypothalamic CRF triggers the rapid release of adrenocorticotropin hormone (ACTH) from the anterior pituitary, leading to the synthesis and secretion of glucocorticoids from the adrenal cortex (Vale et al., 1981). Subsequent actions of glucocorticoids affect a wide range of physiologic and metabolic processes with the primal aim of mobilizing energy stores and...

Delia M Vzquez1 and Seymour Levine2

1 Department of Pediatrics, University of Michigan, 1150 Medical Center Drive, Ann Arbor, Ml 48109-9550, USA Center for Neuroscience, Department of Psychiatry, University of California, Davis, Davis, California, 95616, USA Glossary Maternal deprivation separation of mother and infant during the stress-hyporesponsive period, which needs to last for at least 8h for immediate and persistent effects on the neuroendocrine regulation of the hypothalamic-pituitary-adrenal axis. Stress-hyporesponsive...

Epilogue

The aim of the present paper was to give a comprehensive overview of the differences in the stress system between different strains of rats. Although many different strains of rats have been used in endocrinological and neurobiological research, few large-scale studies have investigated strain differences. Most of the studies have concentrated on investigating the differences between two strains of rats (like F344 vs. LEW or SHR vs. WKY rats) or on two selection lines (like APO-SUS vs....

Influence of glucocorticoids on the behavioral effects of psychostimulant drugs

Glucocorticoids hormones have been shown to play an important role in modulating the behavioral effects of psychostimulant drugs. Studies on the effects of these hormones on drug responding have been performed by modifying glucocorticoid levels and by examining the behavioral consequences of these manipulations. In this section, we will review the role of glucocorticoids on drug-induced behavioral responses, such as locomotor activity, self-administration and relapse. We will mostly focus on...

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Animals exposed to the SPS paradigm show significantly lower plasma ACTH response than naive animals when both groups are pretreated with hydrocortisone and receive restraint stress. These data suggest enhanced negative feedback in the SPS group. Middle panel. MR GR ratio changes within hippocampal subfields, 24h, 7 and 14 days following the SPS, compared to controls. SPS-7 and SPS-14 groups are significantly lower than the controls, while SPS-24h group is significantly...

Info

Radarweg 29, PO Box 211,1000 AE Amsterdam, The Netherlands The Boulevard, Langford Lane, Kidlington, Oxford 0X5 1GB, UK Copyright 2005 Elsevier BY All rights reserved No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means electronic, mechanical, photocopying, recording or otherwise without the prior written permission of the publisher Permissions may be sought directly from Elsevier's Science & Technology Rights Department in...

Introduction

A successful survival for any individual depends on their ability to cope with numerous environmental stressors and challenges. For that purpose, an organism is equipped with a number of regulatory mechanisms. The two main components of the stress system are (1) the HPA (HPA) axis and (2) autonomic nervous system (ANS) (especially the sympathetic branch). The most important central component of the HPA axis is the paraventricular nucleus (PVN) of the hypothalamus (encompassing both...

Israel Liberzon1 Samir Khan2 and Elizabeth A Young3

1Department of Psychiatry, University of Michigan, 1500 E. Medical Ctr Dr UH-9D, Box 0118, Ann Abor MI 48109-0117, USA 2Department of Psychiatry, University of Michigan, VA Med Ctr, Research (11R) 2215 Fuller Road, Ann Arbor MI 48105, USA 3Department of Psychiatry and Mental Health Research Institute 205 Zina Pitcher Place, University of Abstract Posttraumatic stress disorder (PTSD) is a potential consequence of being exposed to or witnessing an event provoking fear, helplessness, or horror. It...

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The effects of vehicle or diazepam (1, 2, 4, and 8mg kg IP) are shown on core body temperature in a stress-induced hyperthermia procedure in three strains of mice (129SvEv, TV 12 Swiss-Webster, TV 12 C57BL 6J, N 2) using continuous telemetric measurement of core body temperature. Each male mouse from each strain randomly obtained vehicle or all doses of diazepam over a 3-week period (at least two washout days between treatments). Animals obtained an intraperitoneal injection of either...

List of Contributors Part

Andrews, Ascend Pharmaceutical Inc., Speakman Drive, Mississauga, ON, Canada M. Bonacina, Department of Internal Medicine and Medical Therapy, University of Pavia, Piazza Borromeo 2, 271000 Pavia, Italy T. Cartmell, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK A.R. Cools, Department of Psychoneuropharmacology, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands S.C. Coste, Department of Molecular...

Lo Oo On

LAD Route Measure Result Comment Reference > 20 p.o. Latency to start t > 3 p.o. open arm time - i.p. Duration vocali- zations Anxiolytic-like, although no single dose was significant Anxiolytic-like, although no single dose was significant No effect under basal conditions Anxiolytic-like under stressful condition No effect on conflict behaviour under basal conditions Anxiolytic-like Anxiolytic-like under basal conditions, but only in the attempts measure Griebel et al, 2000 Griebel et al,...

Michela Marinelli and Pier Yincenzo Piazza

INSERM U.588, Universit de Bordeaux 2, Rue Camille Saint-Sa ns, 33077 Bordeaux Cedex, France Abstract In this review, we examine how differences in the activity of the hypothalamic-pituitary-adrenal (HPA) axis can influence vulnerability to drug addiction. Glucocorticoid hormones, the final step in the activation of the HPA axis, show a basal circadian secretion, and rise in response to stressful events. Studies manipulating levels of glucocorticoids show that these hormones facilitate the...

Os 10 12 14 16 Ib 20 22 24 02

Orcadian course in core body temperature in males of three strains of mice (C57BL 6J, Swiss-Webster and 129SvEv) equipped with telemetric devices to measure body temperature continuously. Animals were well adapted (at least a month) to a 12 12 h light-dark schedule (lights on from 06 00 to 18 00h). The data are collected over a 7-day period of continuous measurement and show the average body temperature over this period. Data are summarized over 30min periods. Fig. 5. Orcadian course in...

Other hypertensive strains

Next to the SHR, several other hypertensive strains have been developed. The inherited stress-induced arterial hypertensive (ISIAH) rat was originally selected from the Wistar strain (Markel, 1992), by selectively breeding animals with a high blood pressure response to restraint stress. However, after selective inbreeding, the animals also developed an increase in basal blood pressure (Maslova et al, 1998, 2002a). Restraint stress produce a significantly larger increase in blood pressure in...

Other rats strains and selection lines

Much less research has been done in other strains. In a recent paper the baseline blood pressure and heart rate of six strains were compared (van den Brandt et al, 1999). The authors found clear differences in blood pressure, with, for instance, F344 rats having a significantly higher systolic and diastolic blood pressure than LEW rats. The same difference is also found for the baseline heart rate. Interestingly, whereas the heart rate show a clear circadian rhythm in the F344 rats, this seems...

Sieglinde Modell and Florian Holsboer

Max Planck Institute of Psychiatry, Kraepelinstra e 2-10, 80804 M nchen, Germany Abstract Depression is characterized by a group of varying symptoms and encompasses a number of clinical diagnosis. External stressors usually trigger the onset of depression and the hypothalamic-pituitary-adrenocortical (HPA) axis is activated. Moreover, genetic influences play a substantial role. A large number of clinical and preclinical studies investigating the stress system in depth have led to the...

Sarah C Coste Susan E Murray and Mary P Stenzel Poore

Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon 97239-3098, USA Abstract The corticotropin-releasing factor (CRF) family constitutes a primary system that mediates adaptive neuroendocrine, autonomic, and behavioral responses to stress, a process known as allostasis. Genetically engineered mice provide a powerful tool for dissection of corticotropin pathways. A collection of models have been generated that harbor specific alterations in...

Strain differences in the autonomic nervous system

In contrast to the wealth of data relating to strain differences in the HPA axis activity, much less data is available with respect to differences in activity of the ANS. This may in part be due to the more complex techniques required for measuring the activity of the ANS. As discussed in the introduction the ANS consists of a sympathetic and a parasympathetic limb and the overall activity depends on the relative strength of both systems. Moreover, the ANS affects virtually all internal organs,...

Stress

-20 -10 0 10 20 30 40 50 60 -20 -10 0 10 20 30 40 50 60 Time (min) STRESSED CONTROLS SSR149415 (30 mg kg po) STRESSED CONTROLS DIAZEPAM (2 mg kg ip) Fig. 6. Effects of the Vlb receptor antagonist, SSR149415, on autonomic markers of the stress response produced by restraint as measured by radiotelemetry. It consists notably of significant elevations of blood pressure and heart rate. SSR149415 and diazepam were administered 60 and 30min prior to restraint, respectively. Data represent mean S.E.M....

The hypothalamicpituitary adrenal axis

Glucocorticoids hormones are the last step of the activation of the HPA axis. Afferent inputs to the hypothalamus induce the release of corticotropin-releasing factor (CRF) CRF reaches the pituitary via the hyphophyseal portal system and activates the release of ACTH in the bloodstream, which, in turn, triggers the secretion of glucocorticoids (Cortisol in humans and corticosterone in rodents) by the cortical part of the adrenal gland (for review, see McEwen et al., 1986). In humans, as in...

Volume

HANDBOOK OF STRESS AND THE BRAIN Part 2 Stress Integrative and Clinical Aspects Previously published in TECHNIQUES IN THE BEHAVIORAL AND NEURAL SCIENCES Volume 1 Feeding and Drinking, by F. Toates and N.E. Rowland (Eds.), 1987, ISBN 0-444-80895-7 Volume 2 Distribution-free Statistics Application-oriented Approach, by J. Krauth, 1988, ISBN 0-444-80934-1, Paperback ISBN 0-444-80988-0 Volume 3 Molecular Neuroanatomy, by F.W. Van Leeuwen, R.M. Buijs, C.W. Pool and O. Pach (Eds.), 1989, ISBN...

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T (metyrapone, f (CRF, IVSA) CRF, IVSA) *Data also refer to studies not reviewed here on the effects of acute and chronic food restriction on IV drug SA and CPP (see Gaiardi et al., 1987 Bell et al., 1997 Carroll, 1999). Abbreviations no effect , decrease f, increase t- inconsistent results or insufficient data to reach a conclusion on the direction of the effect B, binge self-administration (unlimited access) CPP, conditioned place preference CRF, corticotropin-releasing factor DMCM, a...

X10001

Early deprivation in the common marmoset and acute stress endocrinology assessed via urinalysis. (A) Urinary Cortisol response to ED performed in the morning or afternoon on PND 2-28, N 10 ED infants, with urine samples pooled, AM or PM, for pre-ED (basal) and post-ED (90- and 120-min deprivations). In AM urines, pre- and post-ED values did not differ significantly from each other ( (9) 0.19, p > 0.84). whereas in PM urines, post-ED values were significantly greater than pre-ED ( (9)...

Allostasis and allostatic load

In recent years, allostasis and allostatic load have become proverbial terms, owing to their encompassing notion of stress and stress-related pathology. Allostasis refers to the active maintainence of stability of the internal milieu carried out via the initiation of broad shifts in hormonal, behavioral, and autonomic pathways to match a perceived or anticipated challenge (McEwen, 1998 Sterling and Eyer, 1988). Such adaptive changes work well when turned on and off efficiently. Maladaptions in...

Glucocorticoid receptor knockout mice

Two distinct disruptions of the GR gene were generated in mice using standard gene targeting. In one model (GRnu mice), the GR gene is disrupted at exon 3, which encodes a portion of the DNA binding domain. This mutation results in complete inactiva-tion of GR leading to respiratory distress and perinatal mortality caused by severe lung atelectasis (Cole et al, 1995 Kellendonk et al, 1999). Thus, glucocorticoid signaling through GR is critically needed for lung maturation and neonatal survival....

F344 and LEW compared to other rat strains

For F344 and LEW rats have been studied in such great detail, they have also been compared to other inbred and outbred strains. In a series of experiments, Armario and his colleagues investigated the HPA axis sensitivity of F344, LEW, Brown Norway (BN), spontaneous hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, using the forced swim test. They studied both behaviour (struggling and immobility times) and various biochemical parameters. At the behavioural level, WKY and BN showed low levels...

CRFBP knockout mice Crfbp Ko

In addition to CRF-BP transgenic models, a CRF-BP KO mouse was created by targeted gene deletion (Karolyi et al., 1999). These mice would be expected to exhibit overactive CRF pathways, given the lack of a CRF depot. Although no obvious changes in baseline or stress-induced HPA hormones were seen, CRF-BP KO mice display a modest increase in anxiety-related behavior. In addition, CRF-BP KO mice showed alterations in feeding behavior. Male CRF-BP KO mice ate less during the light and dark cycles...

Strain and line differences in the HPA axis Fischer 344 and Lewis rats

Fischer 344 (F344) rats were originally bred at Columbia University in 1920 by Curtiss and Dunning. Lewis (LEW) rats were originally developed by Margaret Lewis from the Wistar strain. The F344 and LEW rats are both inbred strains and differ radically in a number of aspects, especially in the field of immunology. Thus, LEW rats are highly susceptible to many inflammatory agents (Sternberg et al., 1989a,b). However, these animals differ in many other respects as well, especially in relation to...

Lin Lu and Yavin Shaham

Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, NIHjDHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA Abstract Exposure to high levels of life stress is associated with opiate and psychostimulant use in humans, but a causal role has not been established and the mechanisms involved in this putative association are not known. Processes involved in drug addiction can be studied under controlled experimental conditions in laboratory animals,...

Stressrelated disorders

Johnson & Johnson Pharmaceutical Research & Development, a Division of Janssen Pharmaceutica N.V., Turnhoutseweg 30, 2340 Beerse, Belgium Abstract Preclinical and clinical data indicate that corticotropin-releasing factor (CRF) and CRF-related peptides play an important role in stress-related disorders, including psychiatric disorders, such as anxiety disorder, major depression, eating disorders and drug abuse, gastrointestinal disorders, such as irritable bowel syndrome, and...

Rachel Yehuda

Psychiatry Department and Division of Traumatic Stress Studies, Mount Sinai, School of Medicine and Bronx Veterans Affairs, Bronx, NY, USA Abstract This chapter discusses how neuroendocrine findings in posttraumatic stress disorder (PTSD) potentially inform us about hypothalamic -pituitary-adrenal (HPA) alterations in PTSD and highlight alterations relevant to the identification of targets for drug development. The majority of studies demonstrate alterations consistent with an enhanced negative...

CRF type 1 receptor knockout mice CRF receptor KO

CRF, receptor KO mice were generated by two independent groups using targeted gene inactivation in embryonic stem cells (Smith et al., 1998 Timpl et al., 1998). These two lines of mice generally show similar phenotypes despite differences in the genetic background of the embryonic stem cell lineage. Most notably, these mice display severe alterations in HPA axis regulation and marked glucocorticoid deficiency, along with impaired initiation of behavioral responses to stress. Basal HP A axis...

Jeffrey A Lieberman2

1 Duke University School of Medicine and Durham VAMC, Durham, NC 27705, USA -UNC-Chape Hill School of Medicine, Chapel Hill, NC 27599, USA 3Vanderbilt University School of Medicine, Psychiatric Hospital at Vanderbilt, Suite 313, 1601 23rd Avenue South, Nashville, TN 37218, USA Abstract Both preclinical and clinical evidence suggest that atypical antipsychotics may modulate the stress response in a manner that is distinct from conventional agents. For example, atypical antipsychotics have...

Christopher R Pryce Daniela Riiedi Bettschen Andrea C Dettling and Joram Feldon

Dettling Daniela

Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, Abstract Depression is now one of the most common human illnesses and is of immense clinical and economic importance. Considerable preclinical research efforts have been made to establish animal models of depression, and more recently the human evidence derived from brain imaging studies has provided important insights into the functional neuroanatomical correlates of depression. Despite this,...

CRFoverexpressing transgenic mice CRFTg

We created a transgenic model of chronic CRF hypersecretion (CRF-Tg mice) using a chimeric CRF transgene comprised of the metallothionein promoter linked to the rat CRF genomic gene (Stenzel-Poore et al., 1992). These mice exhibit chronic HPA axis activation due to central overproduction of CRF. Basal ACTH is elevated two- to five-fold, resulting in a tenfold elevation in circulating glucocorticoids. Physically, such high corticosterone levels render these mice Cushingoid. By eight weeks of...

Dysregulation of CRF pathways in human disease states

Imbalances of the HPA axis and central CRF pathways have been associated with allostatic load and subsequent pathological states (Schulkin et al., 1998). In the periphery, excess circulating glucocorticoids caused by prolonged activation of the HPA axis or long-term treatment with exogenous glucocorticoids results in Cushing's disease or syndrome (Nelson, 1989). Continued exposure to high levels of glucocorticoids eventually leads to metabolic dysfunction that may include muscle wasting,...

CRF knockout mice CRF KO

Mice deficient in CRF were created using targeted gene inactivation in embryonic stem cells (Muglia et al., 1995). This model has added important information to our present understanding of CRF roles and in some cases has provided evidence that contradicts current hypotheses. CRF KO mice exhibit severe glucocorticoid deficiency and impaired HPA axis activation - features predicted to occur in the absence of CRF. Effects of CRF absence on organ development and longevity Histological examination...

Ptsd

Brief one-time exposure produces long-term effects. Produces conditioned fear responses. Characterized by time-dependent sensitization. Produces enhanced HPA negative feedback. Produces a sustained exaggeration of the acoustic startle response. Exposed animals can be divided into well-adapted and mal-adapted. Single episode can produce sustained behavioral inhibition, perhaps reflective of PTSD-like avoidance. Produces sensitization of LC-noradrenaline neurons. Produces short-term...

Cytokine activation of the hypothalamopituitaryadrenal axis

Crf Hpa Axis

Department of Pharmacology and Therapeutics, Louisiana State University Health Sciences Center. P.O. Box 33932. Shreveport. LA 71103-3932, USA Abstract The discovery that peripheral administration of interleukin-1 (IL-1) to rats potently activated the hypothalamo-pituitary-adrenocortical (HPA) axis, initiated a new understanding of the interactions between the immune system and the brain. It was proposed, and widely accepted that the increase in circulating concentrations of glucocorticoids...

Glucocorticoid receptor antisense knock down

Partial knock-down and tissue-specific mutations of the glucocorticoid receptor have circumvented perinatal mortality and allowed for examination of glucocorticoid pathways in adult physiology. Pepin et al. (1992) created a transgenic mouse model that harbors a transgene that constitutively expresses antisense RNA against GR. To restrict transgene expression to the CNS, a neurofilament promoter was used. Thus, antisense expression impairs production of GR mRNA predominantly in neural tissue,...

Nonpeptide vasopressin Vlb receptor antagonists

Guy Griebel1'* and Claudine Serradeil-Le Gal2 ' Sanofi-Synthelabo Recherche, Bagneux, France 2 Sanofi-Synthelabo Recherche, Toulouse, France Abstract Arginine vasopressin (AVP) is critical for adaptation of the hypothalamo-pituitary-adrenal axis during stress through its ability to potentiate the stimulatory effect of CRF. This observation, taken together with the identification of AVP receptors (e.g. V(b) in limbic structures has led to the idea that this peptide may provide a good opportunity...

Glucocorticoid antagonists and depression

Hpa Dysfunction

NeurAxon Inc., Suite 318, 16-1375 Southdown Road, Mississauga, ON, Canada L5J 2Z1 Abstract Substantial evidence exists to indicate a prominent role for chronically elevated levels of Cortisol and a dysfunctional feedback system within the hypothalamic-pituitary-adrenal (HPA) axis in major depressive disorder. Chronically elevated Cortisol levels are strongly correlated with depression and normalization of Cortisol levels accompanies recovery failure to normalize predicts relapse or poor...

And Lucianne Groenink12

1 Department of Psyehopharmaeology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Utrecht University, Sorbonnelaan 16, 3584CA Utrecht, The Netherlands 2Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands 3Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA Abstract When animals are confronted with a stressor, they respond by an extensive stress response, amongst which a rise in body...

Ssr149415

Chemical structures of SSR149415 ((2S, H-indol-3-yl -4-hydroxy-TV, N-dimethyl-2-pyrrolidine carboxamide, isomer(-)). pituitary adrenocorticotropin (ACTH) secretion (McCann and Brobeck, 1954 Antoni, 1993 Aguilera, 1994). AVP is critical for adaptation of the hypothalamo-pituitary adrenal (HPA) axis during stress through its ability to potentiate the stimulatory effect of CRF. Both acute and repeated stresses (e.g., restraint, foot shocks) stimulate release of AVP from the median eminence...

Substance P NKi receptor antagonists

Substance Headache

Clinical Neuroscience, Merck Research Laboratories, BL2-5, West Point, PA 19486, USA Abstract Stress responses involve changes in hormone secretion, respiration, cardiovascular, and gastrointestinal function, and behavior in order to prepare an organism to respond to perceived or actual danger. They are orchestrated by neural circuits including the amygdala, brainstem, and hypothalamus. Substance P is a peptide neurotransmitter that is expressed within these neural pathways and can activate...

CRF type 2 receptor knockout mice CRF2 receptor KO

The role of CRF2 receptor pathways in stress-related pathways remained elusive until the recent generation of CRF2 receptor KO mice and the development of a specific CRF2 receptor antagonist. In addition, the recent discovery of CRF2 receptor-selective ligands, urocortin 2 and urocortin 3, aid greatly in our understanding of CRF2 receptor pathways. CRF2 receptor KO mice were generated by us Coste et al, 2000 and two other independent groups Bale et al, 2000 Kishimoto et al, 2000 using targeted...

Randall R Sakai and Kellie LK Tamashiro

Department of Psychiatry, University of Cincinnati Medical Center, 2170 E. Ga braith Road, Bldg 43 UC-E, Cincinnati, OH 45237, USA The field of stress research has generated growing interest in response to the escalating number of psychopathologies associated with chronic stress in humans. A better understanding of the mechanisms through which chronic stress leads to these pathologies will enhance the development, effectiveness and efficiency of rational clinical therapies. As such, a variety...