Special Issue "From Synapses to Syndromes in Stress Research: Translational Approaches to the Study of the Neurobiology of Stress-Related Mental Disorders"

Guest Editor
Prof. Dr. David Diamond
¹ Departments of Psychology, Molecular Pharmacology and Physiology, Center for Preclinical and Clinical Research on PTSD, USF Neuroscience Collaborative, University of South Florida, 4202 East Fowler Ave., Tampa, Florida 33620, USA
² Research and Development Service, J.A. Haley Veterans Hospital, 13000 Bruce B. Downs Blvd., Tampa, FL 33612, USA
Website: http://psychology.usf.edu/faculty/diamond/
E-Mail: ddiamond@usf.edu
Phone: +1 813 974 0480
Fax: +1 813 974 4617
Interests: stress; fear; memory; hippocampus; amygdala; frontal cortex; synaptic plasticity; long-term potentiation

Dear Colleagues,

Fear and stress-provoking experiences generate changes in the brain and behavior that can last from minutes to a lifetime. An experience-induced increase in arousal can have a constructive outcome, producing an enhancement of memory for important events and an improvement in behavioral performance. However, intense fear-provoking experiences can generate pathological outcomes. Traumatic stress contributes to the development of debilitating mood and anxiety disorders, including depression and post-traumatic stress disorder, and has been associated with a broad range of mental and neurodegenerative disorders, including Alzheimer’s disease, phobias, schizophrenia and multiple sclerosis. This special issue of Behavioral Sciences targets a broad range of research addressing the effects of stress on brain, behavior and mental disease at mechanistic, preclinical and clinical levels of analysis.

Prof. Dr. David Diamond
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Behavioral Sciences is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. For the first couple of issues the Article Processing Charge (APC) will be waived for well-prepared manuscripts. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

Therese A. Kosten and Mindy J. D. Miserendino Article: Stress Alters the Discriminative Stimulus and Response Rate Effects of Cocaine Differentially in Lewis and Fischer Inbred Rats Behav. Sci. 2012, 2(1), 23-37; doi:10.3390/bs2010023 Received: 19 January 2012; in revised form: 9 February 2012 / Accepted: 17 February 2012 / Published: 1 March 2012 Show/Hide Abstract | Download PDF Full-text (367 KB) Abstract: Stress enhances the behavioral effects of cocaine, perhaps via hypothalamic-pituitary-adrenal (HPA) axis activity. Yet, compared to Fischer 344 (F344) rats, Lewis rats have hyporesponsive HPA axis function and more readily acquire cocaine self-administration. We hypothesized that stress would differentially affect cocaine behaviors in these strains. The effects of three stressors on the discriminative stimulus and response rate effects of cocaine were investigated. Rats of both strains were trained to discriminate cocaine (10 mg/kg) from saline using a two-lever, food-reinforced (FR10) procedure. Immediately prior to cumulative dose (1, 3, 10 mg/kg cocaine) test sessions, rats were restrained for 15-min, had 15-min of footshock in a distinct context, or were placed in the shock-paired context. Another set of F344 and Lewis rats were tested similarly except they received vehicle injections to test if stress substituted for cocaine. Most vehicle-tested rats failed to respond after stressor exposures. Among cocaine-tested rats, restraint stress enhanced cocaine’s discriminative stimulus effects in F344 rats. Shock and shock-context increased response rates in Lewis rats. Stress-induced increases in corticosterone levels showed strain differences but did not correlate with behavior. These data suggest that the behavioral effects of cocaine can be differentially affected by stress in a strain-selective manner.

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Robert S. Thompson, Paul V. Strong and Monika Fleshner Article: Physiological Consequences of Repeated Exposures to Conditioned Fear Behav. Sci. 2012, 2(2), 57-78; doi:10.3390/bs2020057 Received: 5 April 2012; in revised form: 5 May 2012 / Accepted: 14 May 2012 / Published: 18 May 2012 Show/Hide Abstract | Download PDF Full-text (1932 KB) | View HTML Full-text | Download PMC-XML Full-text Abstract: Activation of the stress response evokes a cascade of physiological reactions that may be detrimental when repeated or chronic, and when triggered after exposure to psychological/emotional stressors. Investigation of the physiological mechanisms responsible for the health damaging effects requires animal paradigms that repeatedly evoke a response to psychological/emotional stressors. To this end, adult male Sprague Dawley rats were repeatedly exposed (2X per day for 20 days) to a context that they were conditioned to fear (conditioned fear test, CFT). Repeated exposure to CFT produced body weight loss, adrenal hypertrophy, thymic involution, and basal corticosterone elevation. In vivo biotelemetry measures revealed that CFT evokes sympathetic nervous system driven increases in heart rate (HR), mean arterial pressure (MAP), and core body temperature. Extinction of behavioral (freezing) and physiological responses to CFT was prevented using minimal reinstatement footshock. MAP responses to the CFT did not diminish across 20 days of exposure. In contrast, HR and cardiac contractility responses declined by day 15, suggesting a shift toward vascular-dominated MAP (a pre-clinical marker of CV dysfunction). Flattened diurnal rhythms, common to stress-related mood/anxiety disorders, were found for most physiological measures. Thus, repeated CFT produces adaptations indicative of the health damaging effects of psychological/emotional stress.

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Reto Bisaz and Regina M. Sullivan Review: Developmental Neurobiology of the Rat Attachment System and Its Modulation by Stress Behav. Sci. 2012, 2(2), 79-102; doi:10.3390/bs2020079 Received: 31 March 2012; in revised form: 8 May 2012 / Accepted: 10 May 2012 / Published: 18 May 2012 Show/Hide Abstract | Download PDF Full-text (350 KB) | View HTML Full-text | Download PMC-XML Full-text Abstract: Stress is a powerful modulator of brain structure and function. While stress is beneficial for survival, inappropriate stress dramatically increases the risk of physical and mental health problems, particularly when experienced during early developmental periods. Here we focus on the neurobiology of the infant rat’s odor learning system that enables neonates to learn and approach the maternal odor and describe the unique role of the stress hormone corticosterone in modulating this odor approach learning across development. During the first nine postnatal days, this odor approach learning of infant rats is supported by a wide range of sensory stimuli and ensures attachment to the mother’s odor, even when interactions with her are occasionally associated with pain. With maturation and the emergence of a stress- or pain-induced corticosterone response, this odor approach learning terminates and a more adult-like amygdala-dependent fear/avoidance learning emerges. Strikingly, the odor approach and attenuated fear learning of older pups can be re-established by the presence of the mother, due to her ability to suppress her pups’ corticosterone release and amygdala activity. This suggests that developmental changes in stress responsiveness and the stimuli that produce a stress response might be critically involved in optimally adapting the pup’s attachment system to its respective ecological niche.

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Manuscirpt ID: behavsci-14936
Type of Paper: Article
Title: Stress Alters the Discriminative Stimulus and Response Rate Effects of Cocaine Differentially in Lewis and Fischer Inbred Rats
Authors: Therese Kosten *, Mindy Miserendino
Affiliation: Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Michael E Debakey VAMC, 2002 Holcombe Blvd., Houston, TX 77030, USA; E-Mail: tkosten@bcm.edu
Abstract: Rationale: Acute stress enhances the behavioral effects of cocaine perhaps by additive effects on hypothalamic-pituitary-adrenal (HPA) axis activity.  Yet, compared to Fischer 344 (F344) rats, Lewis rats have hyporesponsive HPA axis function and more readily acquire cocaine self-administration.  Thus, we hypothesized that acute stress would have differential effects on cocaine behaviors in these strains.  Objectives: The effects of three acute stressors on the discriminative stimulus and response rate effects of cocaine were investigated.  Methods: Rats were trained to discriminate cocaine (10 mg/kg) from saline using a two-lever, food-reinforced (FR10) procedure.  Immediately prior to cumulative test (1, 3, 10 mg/kg cocaine) sessions, rats were restrained for 15-min, had 15-min of footshock in a visually distinct context, or were placed in the shock context after several shock+context pairings. Results: Restraint stress enhanced the discriminative stimulus effects of cocaine in F344 rats.  Shock and shock context increased response rates in Lewis rats.  Corticosterone levels were enhanced by all stressors in both strains, but did not correlate with either behavior. Conclusions: These data suggest that the behavioral effects of cocaine can be differentially affected by stress in a strain-selective manner.

Type of Paper: Article
Title: Cotinine, A Forgotten Relative of Nicotine: Self-Medication behind Tobacco Consumption in Psychiatric Disorders
Authors: Valentina Echeverria ^1,2,3 and J. Alex Grizzell 1
Affiliations: ¹ VA Healthcare System, Research & Development, 10,000 Bay Pines Blvd, Bldg 22, Rm123, Bay Pines, FL 33744, USA; E-Mail: Valentina.Echeverria@va.gov
² VA Healthcare system, Tampa, FL, USA
³ Department of Molecular Medicine, University of South Florida, 4202 E. Fowler Avenue, Tampa, FL 33620, USA
Abstract: A greater incidence of tobacco consumption occurs among individuals with psychiatric conditions including posttraumatic stress disorder (PTSD), bipolar disorder, major depression, and schizophrenia than the general population. It has been postulated that smoking is often a form of self-medication to reduce psychiatric symptoms among individuals with these disorders. Most attention has been directed toward nicotine in the attempts to understand the pharmacological agent(s) within tobacco inducing the smoking behavior.  In recent years, new evidence has shown that cotinine, the main metabolite of nicotine, has beneficial effects over psychiatric symptoms and may therefore be promoting tobacco use in this population. These beneficial effects include the inhibition of fear-induced anxiety, working memory enhancement, a facilitation of fear memory extinction and the decrease of contextual fear memory reconsolidation and stability. Cotinine, which accumulates in the body as a result of tobacco exposure, crosses the blood-brain barrier, has a long half-life (19-24 h). Cotinine has differential pharmacological properties than nicotine including its capacity to enhance fear extinction, the absence of addictive or cardiovascular effects in humans at doses in plasma ten-times higher than the ones reached by heavy smoking. In this review, we discuss the pharmacological effects of cotinine and its involvement in tobacco smoking behavior in people suffering from psychiatric conditions.

Type of Paper: Article
Title: Symptom Persistence and Memory Performance in Posttraumatic Stress Disorder: A Gene X Environment Pilot Study
Authors: Annie-Claude David ^{1, 2}, Geeta A. Thakur ^2,3, Vivian Akerib ², Jorge Armony ^2,3, Isabelle Rouleau ¹ and Alain Brunet ^{2, 3, *}
Affiliations: ¹ Université du Québec à Montréal, Canada
² Douglas Mental Health University Institute, Montreal, Canada
³ McGill University, Montreal, Canada
* Corresponding author: Dr. A. Brunet, Ph.D., 6875 LaSalle Boulevard, Montréal (QC), H4H 1R3, Canada. Tel.: 514-761-6131 x2375, Fax: 514-762-3049. E-Mail: alain.brunet@mcgill.ca
Abstract: Most studies examining the relationship between posttraumatic stress disorder (PTSD) and the FKBP5 gene have failed to distinguish between the development and persistence of PTSD. The goal of the present study was to examine the association between four single-nucleotide polymorphisms (SNPs) in the FKBP5 gene (rs3800373, rs9470080, rs1360780, and rs9296158), persistence of PTSD, and endophenotypes such as memory performance. Twenty-two treatment-seekers with acute PTSD were assessed longitudinally 6 months later for PTSD symptom severity and diagnosis as well as memory performance. Results showed that the four SNPs interacted with improvement in PTSD symptoms as well as PTSD diagnostic status. People homozygous for the dominant allele and experiencing higher levels of peritraumatic responses also showed more memory dysfunction. The results of this study suggest that SNPs in the FKBP5 gene are associated with symptom persistence and memory performance in acute PTSD.