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GR-owing Up Stressed: Implications for Anxiety and Addiction

  • Scott J. Russo
    Correspondence
    Address correspondence to Scott J. Russo, Ph.D., Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York 10029
    Affiliations
    Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York
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      Early life adversity is known to have profound effects on the development and function of neural circuits that control emotional behaviors (
      • McEwen B.S.
      Physiology and neurobiology of stress and adaptation: central role of the brain.
      ). The result in humans is a greatly enhanced predisposition to develop depression and anxiety disorders or addiction throughout the individual's lifetime. Rodent models of chronic stress have begun to identify the critical periods of early life adversity along with the brain circuits and molecules that control pathologic behaviors relevant to these psychiatric disorders. In this issue, Wei et al. (
      • Wei Q.
      • Fentress H.M.
      • Hoversten M.T.
      • Zhang L.
      • Hebda-Bauer E.K.
      • Watson S.J.
      • et al.
      Early-life forebrain glucocorticoid receptor overexpression increases anxiety behavior and cocaine sensitization.
      ) provides new evidence for a critical window before weaning, whereby increased levels of glucocorticoid receptors (GRs) in the forebrain lead to lifelong increases in exploratory-based anxiety behavior and cocaine-induced locomotor sensitization. Associated with these behavioral changes are vast lifelong transcriptional changes in the dentate gyrus of the hippocampus (hipp) and, to a lesser extent, the nucleus accumbens (NAc), brain structures critically involved in stress disorders and addiction. These data highlight the potential importance of developmental experience in controlling normal brain function and behavior in adulthood.
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      Linked Article

      • Early-Life Forebrain Glucocorticoid Receptor Overexpression Increases Anxiety Behavior and Cocaine Sensitization
        Biological PsychiatryVol. 71Issue 3
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          Genetic factors and early-life adversity are critical in the etiology of mood disorders and substance abuse. Because of their role in the transduction of stress responses, glucocorticoid hormones and their receptors could serve as both genetic factors and mediators of environmental influences. We have shown that constitutive overexpression of the glucocorticoid receptor (GR) in forebrain results in increased emotional reactivity and lability in mice. Here, we asked whether there was a critical period for the emergence of this phenotype.
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