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      Stress and the dopaminergic reward system

      review-article
      Experimental & Molecular Medicine
      Nature Publishing Group UK
      Molecular neuroscience, Motivation

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          Abstract

          Dopamine regulates reward-related behavior through the mesolimbic dopaminergic pathway. Stress affects dopamine levels and dopaminergic neuronal activity in the mesolimbic dopamine system. Changes in mesolimbic dopaminergic neurotransmission are important for coping with stress, as they allow adaption to behavioral responses to various environmental stimuli. Upon stress exposure, modulation of the dopaminergic reward system is necessary for monitoring and selecting the optimal process for coping with stressful situations. Aversive stressful events may negatively regulate the dopaminergic reward system, perturbing reward sensitivity, which is closely associated with chronic stress-induced depression. The mesolimbic dopamine system is excited not only by reward but also by aversive stressful stimuli, which adds further intriguing complexity to the relationship between stress and the reward system. This review focuses on lines of evidence related to how stress, especially chronic stress, affects the mesolimbic dopamine system, and discusses the role of the dopaminergic reward system in chronic stress-induced depression.

          Neuroscience: finding reward in stressful situations

          The brain’s response to stressful conditions is linked to mechanisms for processing rewarding stimuli, but the nature of this connection remains poorly understood. Studies indicate that how animals cope with acute or chronic stress relies in part on dopamine, a neurotransmitter that produces ‘reward’ signals in the brain. Ja-Hyun Baik, Korea University, Seoul, South Korea, reviews how stress influences dopamine-mediated signaling, in particular exploring the hypothesis that the nature of stressful stimuli specifically determines the behavior induced by dopamine and the way signals are perceived in terms of stress or reward. However, the author also notes the many unanswered questions around the neurological mechanisms underlying chronic stress, and the depression and lack of pleasure produced by stress. Further research is needed to understand the role of dopamine signaling.

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          Most cited references107

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          Stress, Adaptation, and Disease: Allostasis and Allostatic Load

          Adaptation in the face of potentially stressful challenges involves activation of neural, neuroendocrine and neuroendocrine-immune mechanisms. This has been called "allostasis" or "stability through change" by Sterling and Eyer (Fisher S., Reason J. (eds): Handbook of Life Stress, Cognition and Health. J. Wiley Ltd. 1988, p. 631), and allostasis is an essential component of maintaining homeostasis. When these adaptive systems are turned on and turned off again efficiently and not too frequently, the body is able to cope effectively with challenges that it might not otherwise survive. However, there are a number of circumstances in which allostatic systems may either be overstimulated or not perform normally, and this condition has been termed "allostatic load" or the price of adaptation (McEwen and Stellar, Arch. Int. Med. 1993; 153: 2093.). Allostatic load can lead to disease over long periods. Types of allostatic load include (1) frequent activation of allostatic systems; (2) failure to shut off allostatic activity after stress; (3) inadequate response of allostatic systems leading to elevated activity of other, normally counter-regulated allostatic systems after stress. Examples will be given for each type of allostatic load from research pertaining to autonomic, CNS, neuroendocrine, and immune system activity. The relationship of allostatic load to genetic and developmental predispositions to disease is also considered.
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            Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress.

            Mice experiencing repeated aggression develop a long-lasting aversion to social contact, which can be normalized by chronic, but not acute, administration of antidepressant. Using viral-mediated, mesolimbic dopamine pathway-specific knockdown of brain-derived neurotrophic factor (BDNF), we showed that BDNF is required for the development of this experience-dependent social aversion. Gene profiling in the nucleus accumbens indicates that local knockdown of BDNF obliterates most of the effects of repeated aggression on gene expression within this circuit, with similar effects being produced by chronic treatment with antidepressant. These results establish an essential role for BDNF in mediating long-term neural and behavioral plasticity in response to aversive social experiences.
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              Modulation of striatal projection systems by dopamine.

              The basal ganglia are a chain of subcortical nuclei that facilitate action selection. Two striatal projection systems--so-called direct and indirect pathways--form the functional backbone of the basal ganglia circuit. Twenty years ago, investigators proposed that the striatum's ability to use dopamine (DA) rise and fall to control action selection was due to the segregation of D(1) and D(2) DA receptors in direct- and indirect-pathway spiny projection neurons. Although this hypothesis sparked a debate, the evidence that has accumulated since then clearly supports this model. Recent advances in the means of marking neural circuits with optical or molecular reporters have revealed a clear-cut dichotomy between these two cell types at the molecular, anatomical, and physiological levels. The contrast provided by these studies has provided new insights into how the striatum responds to fluctuations in DA signaling and how diseases that alter this signaling change striatal function.
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                Author and article information

                Contributors
                jahyunb@korea.ac.kr
                Journal
                Exp Mol Med
                Exp Mol Med
                Experimental & Molecular Medicine
                Nature Publishing Group UK (London )
                1226-3613
                2092-6413
                1 December 2020
                1 December 2020
                December 2020
                : 52
                : 12
                : 1879-1890
                Affiliations
                GRID grid.222754.4, ISNI 0000 0001 0840 2678, Molecular Neurobiology Laboratory, Department of Life Sciences, , Korea University, ; Seoul, 02841 South Korea
                Author information
                http://orcid.org/0000-0002-4607-924X
                Article
                532
                10.1038/s12276-020-00532-4
                8080624
                33257725
                0490c8d3-9bff-44df-a4fe-289e66fdaac5
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 30 August 2020
                : 12 October 2020
                : 12 October 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100003725, National Research Foundation of Korea (NRF);
                Award ID: 2016M3A9D5A01952412
                Award ID: 2013M3A9D5072550
                Award ID: 2017R1A2B4008875
                Award ID: 2015R1A5A1009024
                Award ID: 2020R1A2C2101010
                Award Recipient :
                Categories
                Review Article
                Custom metadata
                © The Author(s) 2020

                Molecular medicine
                molecular neuroscience,motivation
                Molecular medicine
                molecular neuroscience, motivation

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