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      Activation of Basolateral Amygdala to Nucleus Accumbens Projection Neurons Attenuates Chronic Corticosterone-Induced Behavioral Deficits in Male Mice

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          Abstract

          The basolateral amygdala (BLA) is critical for reward behaviors via a projection to the nucleus accumbens (NAc). Specifically, BLA-NAc projections are involved in reinforcement learning, reward-seeking, sustained instrumental responding, and risk behaviors. However, it remains unclear whether chronic stress interacts with BLA-NAc projection neurons to result in maladaptive behaviors. Here we take a chemogenetic, projection-specific approach to clarify how NAc-projecting BLA neurons affect avoidance, reward, and feeding behaviors in male mice. Then, we examine whether chemogenetic activation of NAc-projecting BLA neurons attenuates the maladaptive effects of chronic corticosterone (CORT) administration on these behaviors. CORT mimics the behavioral and neural effects of chronic stress exposure. We found a nuanced role of BLA-NAc neurons in mediating reward behaviors. Surprisingly, activation of BLA-NAc projections rescues CORT-induced deficits in the novelty suppressed feeding, a behavior typically associated with avoidance. Activation of BLA-NAc neurons also increases instrumental reward-seeking without affecting free-feeding in chronic CORT mice. Taken together, these data suggest that NAc-projecting BLA neurons are involved in chronic CORT-induced maladaptive reward and motivation behaviors.

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          Stress and depression.

          Improved methods of assessment and research design have established a robust and causal association between stressful life events and major depressive episodes. The chapter reviews these developments briefly and attempts to identify gaps in the field and new directions in recent research. There are notable shortcomings in several important topics: measurement and evaluation of chronic stress and depression; exploration of potentially different processes of stress and depression associated with first-onset versus recurrent episodes; possible gender differences in exposure and reactivity to stressors; testing kindling/sensitization processes; longitudinal tests of diathesis-stress models; and understanding biological stress processes associated with naturally occurring stress and depressive outcomes. There is growing interest in moving away from unidirectional models of the stress-depression association, toward recognition of the effects of contexts and personal characteristics on the occurrence of stressors, and on the likelihood of progressive and dynamic relationships between stress and depression over time-including effects of childhood and lifetime stress exposure on later reactivity to stress.
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            Toward the future of psychiatric diagnosis: the seven pillars of RDoC

            Background Current diagnostic systems for mental disorders rely upon presenting signs and symptoms, with the result that current definitions do not adequately reflect relevant neurobiological and behavioral systems - impeding not only research on etiology and pathophysiology but also the development of new treatments. Discussion The National Institute of Mental Health began the Research Domain Criteria (RDoC) project in 2009 to develop a research classification system for mental disorders based upon dimensions of neurobiology and observable behavior. RDoC supports research to explicate fundamental biobehavioral dimensions that cut across current heterogeneous disorder categories. We summarize the rationale, status and long-term goals of RDoC, outline challenges in developing a research classification system (such as construct validity and a suitable process for updating the framework) and discuss seven distinct differences in conception and emphasis from current psychiatric nosologies. Summary Future diagnostic systems cannot reflect ongoing advances in genetics, neuroscience and cognitive science until a literature organized around these disciplines is available to inform the revision efforts. The goal of the RDoC project is to provide a framework for research to transform the approach to the nosology of mental disorders.
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              Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression.

              Understanding the physiopathology of affective disorders and their treatment relies on the availability of experimental models that accurately mimic aspects of the disease. Here we describe a mouse model of an anxiety/depressive-like state induced by chronic corticosterone treatment. Furthermore, chronic antidepressant treatment reversed the behavioral dysfunctions and the inhibition of hippocampal neurogenesis induced by corticosterone treatment. In corticosterone-treated mice where hippocampal neurogenesis is abolished by X-irradiation, the efficacy of fluoxetine is blocked in some, but not all, behavioral paradigms, suggesting both neurogenesis-dependent and -independent mechanisms of antidepressant action. Finally, we identified a number of candidate genes, the expression of which is decreased by chronic corticosterone and normalized by chronic fluoxetine treatment selectively in the hypothalamus. Importantly, mice deficient in one of these genes, beta-arrestin 2, displayed a reduced response to fluoxetine in multiple tasks, suggesting that beta-arrestin signaling is necessary for the antidepressant effects of fluoxetine.
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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
                24 February 2021
                2021
                : 15
                : 643272
                Affiliations
                [1] 1Neuroscience Graduate Program, Rutgers, The State University of New Jersey , Piscataway, NJ, United States
                [2] 2Department of Psychology, Behavioral and Systems Neuroscience, Rutgers, The State University of New Jersey , Piscataway, NJ, United States
                Author notes

                Edited by: Robert Warren Gould, Wake Forest School of Medicine, United States

                Reviewed by: Jacqueline M. Barker, Drexel University, United States; Jasper Heinsbroek, University of Colorado, United States

                *Correspondence: Benjamin A. Samuels ben.samuels@ 123456rutgers.edu

                Specialty section: This article was submitted to Motivation and Reward, a section of the journal Frontiers in Behavioral Neuroscience

                Article
                10.3389/fnbeh.2021.643272
                7943928
                33716685
                e07db021-c84e-4fb2-b364-3e19bbcb7fd3
                Copyright © 2021 Dieterich, Floeder, Stech, Lee, Srivastava, Barker and Samuels.

                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
                : 17 December 2020
                : 28 January 2021
                Page count
                Figures: 3, Tables: 0, Equations: 5, References: 77, Pages: 13, Words: 9951
                Funding
                Funded by: National Institute of Mental Health 10.13039/100000025
                Categories
                Behavioral Neuroscience
                Original Research

                Neurosciences
                basolateral amygdala,nucleus accumbens,instrumental behavior,depression models,chronic stress,reward,motivation

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