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      Wistar Kyoto Rats Display Anhedonia In Consumption but Retain Some Sensitivity to the Anticipation of Palatable Solutions

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          Abstract

          The Wistar Kyoto (WKY) rat has been proposed as a model of depression-like symptoms. However, anhedonia—a reduction in the response to normatively rewarding events—as a central depression symptom has yet to be fully assessed in this model. We compared WKY rats and Wistar controls, with stress-susceptibility examined by applying mild unpredictable stress to a subset of each group. Anhedonia-like behavior was assessed using microstructural analysis of licking behavior, where mean lick cluster size reflects hedonic responses. This was combined with tests of anticipatory contrast, where the consumption of a moderately palatable solution (4% sucrose) is suppressed in anticipation of a more palatable solution (32% sucrose). WKY rats displayed greatly attenuated hedonic reactions to sucrose overall, although their reactions retained some sensitivity to differences in sucrose concentration. They displayed normal reductions in consumption in anticipatory contrast, although the effect of contrast on hedonic reactions was greatly blunted. Mild stress produced overall reductions in sucrose consumption, but this was not exacerbated in WKY rats. Moreover, mild stress did not affect hedonic reactions or the effects of contrast. These results confirm that the WKY substrain expresses a direct behavioral analog of anhedonia, which may have utility for increasing mechanistic understanding of depression symptoms.

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          The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R).

          Uncertainties exist about prevalence and correlates of major depressive disorder (MDD). To present nationally representative data on prevalence and correlates of MDD by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and on study patterns and correlates of treatment and treatment adequacy from the recently completed National Comorbidity Survey Replication (NCS-R). Face-to-face household survey conducted from February 2001 to December 2002. The 48 contiguous United States. Household residents ages 18 years or older (N = 9090) who responded to the NCS-R survey. Prevalence and correlates of MDD using the World Health Organization's (WHO) Composite International Diagnostic Interview (CIDI), 12-month severity with the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR), the Sheehan Disability Scale (SDS), and the WHO disability assessment scale (WHO-DAS). Clinical reinterviews used the Structured Clinical Interview for DSM-IV. The prevalence of CIDI MDD for lifetime was 16.2% (95% confidence interval [CI], 15.1-17.3) (32.6-35.1 million US adults) and for 12-month was 6.6% (95% CI, 5.9-7.3) (13.1-14.2 million US adults). Virtually all CIDI 12-month cases were independently classified as clinically significant using the QIDS-SR, with 10.4% mild, 38.6% moderate, 38.0% severe, and 12.9% very severe. Mean episode duration was 16 weeks (95% CI, 15.1-17.3). Role impairment as measured by SDS was substantial as indicated by 59.3% of 12-month cases with severe or very severe role impairment. Most lifetime (72.1%) and 12-month (78.5%) cases had comorbid CIDI/DSM-IV disorders, with MDD only rarely primary. Although 51.6% (95% CI, 46.1-57.2) of 12-month cases received health care treatment for MDD, treatment was adequate in only 41.9% (95% CI, 35.9-47.9) of these cases, resulting in 21.7% (95% CI, 18.1-25.2) of 12-month MDD being adequately treated. Sociodemographic correlates of treatment were far less numerous than those of prevalence. Major depressive disorder is a common disorder, widely distributed in the population, and usually associated with substantial symptom severity and role impairment. While the recent increase in treatment is encouraging, inadequate treatment is a serious concern. Emphasis on screening and expansion of treatment needs to be accompanied by a parallel emphasis on treatment quality improvement.
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            Sex differences in stress-related psychiatric disorders: neurobiological perspectives.

            Stress is associated with the onset and severity of several psychiatric disorders that occur more frequently in women than men, including posttraumatic stress disorder (PTSD) and depression. Patients with these disorders present with dysregulation of several stress response systems, including the neuroendocrine response to stress, corticolimbic responses to negatively valenced stimuli, and hyperarousal. Thus, sex differences within their underlying circuitry may explain sex biases in disease prevalence. This review describes clinical studies that identify sex differences within the activity of these circuits, as well as preclinical studies that demonstrate cellular and molecular sex differences in stress responses systems. These studies reveal sex differences from the molecular to the systems level that increase endocrine, emotional, and arousal responses to stress in females. Exploring these sex differences is critical because this research can reveal the neurobiological underpinnings of vulnerability to stress-related psychiatric disorders and guide the development of novel pharmacotherapies.
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              Chronic Unpredictable Mild Stress for Modeling Depression in Rodents:Meta-analysis of Model Reliability

              Depression is currently among the top five leading causes of the global burden of disease. Chronic unpredictable mild stress (CUMS) is currently the most commonly used, reliable, and effective rodent model of depression. However, for unclear reasons, this protocol is often difficult to reproduce in different laboratories. We performed a meta-analysis of studies that used the CUMS paradigm to evaluate depressive-like behavior in rodents. We sought to identify strain-dependent susceptibility to stress based on the development of one of the main end points of the model, "anhedonia." The meta-analysis indicated that the CUMS protocol is a robust animal model of depression and is strongly associated with anhedonic behavior in rodents. However, high heterogeneity was found in the single subgroup analysis, which was attributable to modification of the CUMS and sucrose preference protocols. This may explain difficulties in reproducing stress protocols by different research groups.
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                Author and article information

                Contributors
                Journal
                Front Behav Neurosci
                Front Behav Neurosci
                Front. Behav. Neurosci.
                Frontiers in Behavioral Neuroscience
                Frontiers Media S.A.
                1662-5153
                03 June 2020
                2020
                : 14
                : 70
                Affiliations
                [1] 1School of Psychology, Cardiff University , Cardiff, United Kingdom
                [2] 2Lilly Research Centre, Eli Lilly & Co. Ltd. , Erl Wood Manor, United Kingdom
                Author notes

                Edited by: Christian P. Müller, University of Erlangen Nuremberg, Germany

                Reviewed by: Kevin Pang, VA New Jersey Health Care System, United States; Carla Gambarana, University of Siena, Italy

                *Correspondence: Dominic M. Dwyer dwyerdm@ 123456cardiff.ac.uk

                Specialty section: This article was submitted to Pathological Conditions, a section of the journal Frontiers in Behavioral Neuroscience

                Article
                10.3389/fnbeh.2020.00070
                7283460
                32581735
                5078db61-2970-4a16-a5c5-8de85a749a3f
                Copyright © 2020 Wright, Gilmour and Dwyer.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 23 December 2019
                : 17 April 2020
                Page count
                Figures: 6, Tables: 0, Equations: 58, References: 99, Pages: 15, Words: 11854
                Funding
                Funded by: Biotechnology and Biological Sciences Research Council 10.13039/501100000268
                Categories
                Behavioral Neuroscience
                Original Research

                Neurosciences
                wky,depression,anhedonia,consummatory,anticipatory,contrast
                Neurosciences
                wky, depression, anhedonia, consummatory, anticipatory, contrast

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