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

Vaishnav Krishnan, Ming Hu Han, Danielle L. Graham, Olivier Berton, William Renthal, Scott J. Russo, Quincey LaPlant, Ami Graham, Michael Lutter, Diane C. Lagace, Subroto Ghose, Robin Reister, Paul Tannous, Thomas A. Green, Rachael L. Neve, Sumana Chakravarty, Arvind Kumar, Amelia J. Eisch, David W. Self, Francis S. LeeCarol A. Tamminga, Donald C. Cooper, Howard K. Gershenfeld, Eric J. Nestler

Research output: Contribution to journalArticlepeer-review

1622 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)391-404
Number of pages14
Issue number2
StatePublished - Oct 19 2007
Externally publishedYes



ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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