Article

Molecular Adaptations Underlying Susceptibility and Resistance to Social Defeat in Brain Reward Regions

Department of Psychiatry, The University of Texas Southwestern Medical Center (UTSWMC), 5323 Harry Hines Boulevard, Dallas, TX 75390-9070, USA.
Cell (Impact Factor: 33.12). 11/2007; 131(2):391-404. DOI: 10.1016/j.cell.2007.09.018
Source: PubMed

ABSTRACT While stressful life events are an important cause of psychopathology, most individuals exposed to adversity maintain normal psychological functioning. The molecular mechanisms underlying such resilience are poorly understood. Here, we demonstrate that an inbred population of mice subjected to social defeat can be separated into susceptible and unsusceptible subpopulations that differ along several behavioral and physiological domains. By a combination of molecular and electrophysiological techniques, we identify signature adaptations within the mesolimbic dopamine circuit that are uniquely associated with vulnerability or insusceptibility. We show that molecular recapitulations of three prototypical adaptations associated with the unsusceptible phenotype are each sufficient to promote resistant behavior. Our results validate a multidisciplinary approach to examine the neurobiological mechanisms of variations in stress resistance, and illustrate the importance of plasticity within the brain's reward circuits in actively maintaining an emotional homeostasis.

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Available from: Olivier Berton, Aug 25, 2015
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    • "For example, the responses to stress vary substantially among individuals, including animals and humans. Some may exhibit resilience, whereas others may exhibit MDDlike vulnerability after the same stress exposure (Krishnan et al., 2007). In addition, the effectiveness of antidepressants in treating MDD varies among individuals (Trivedi et al., 2006), while the predominant clinical manifestations, severity, or courses differ markedly among individuals (Rush, 2007), which has prompted physicians to subtype this disorder (Harald and Gordon, 2012). "
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    Frontiers in Behavioral Neuroscience 05/2015; 9(119):1-13. DOI:10.3389/fnbeh.2015.00119 · 4.16 Impact Factor
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    • "Multiple animal models of depressiondincluding chronic unpredictable stress, chronic social defeat stress, and early life stressdrecapitulate neuroendocrine abnormalities found in patients, including blunted glucocorticoid oscillations , elevated glucocorticoid activity, and disrupted circadian troughs (Willner, 1997; Meaney, 2001; Krishnan et al., 2007; Nestler and Hyman, 2010). In at least one study, blunted circadian cycling was linked specifically to stress susceptibility: circadian rhythm amplitudes were blunted only in mice that exhibited a vulnerable behavioral phenotype in response to chronic social defeat stress, relative to resilient mice that did not develop depression-like symptoms (Krishnan et al., 2007). "
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    • "e ventral tegmental area promotes reward sensitivity and presumably reward learning ( Koo et al . , 2012 ) . Moreover , depressive - like behaviors induced by chronic exposure to stressors are related to lower BDNF levels in the hippocampus , but higher BDNF levels in the ventral tegmental area and the nucleus accumbens [ ( Berton et al . , 2006 ; Krishnan et al . , 2007 ) ; see also ( Yu and Chen , 2011 ) ] ."
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