title: Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions.
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.
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center (UTSWMC), 5323 Harry Hines Boulevard, Dallas, TX 75390-9070, USA.
authors.forename: Vaishnav
authors.initials: V
authors.lastname: Krishnan
authors.forename: Ming-Hu
authors.initials: MH
authors.lastname: Han
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Graham
authors.forename: Olivier
authors.initials: O
authors.lastname: Berton
authors.forename: William
authors.initials: W
authors.lastname: Renthal
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Russo
authors.forename: Quincey
authors.initials: Q
authors.lastname: Laplant
authors.forename: Ami
authors.initials: A
authors.lastname: Graham
authors.forename: Michael
authors.initials: M
authors.lastname: Lutter
authors.forename: Diane C
authors.initials: DC
authors.lastname: Lagace
authors.forename: Subroto
authors.initials: S
authors.lastname: Ghose
authors.forename: Robin
authors.initials: R
authors.lastname: Reister
authors.forename: Paul
authors.initials: P
authors.lastname: Tannous
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Green
authors.forename: Rachael L
authors.initials: RL
authors.lastname: Neve
authors.forename: Sumana
authors.initials: S
authors.lastname: Chakravarty
authors.forename: Arvind
authors.initials: A
authors.lastname: Kumar
authors.forename: Amelia J
authors.initials: AJ
authors.lastname: Eisch
authors.forename: David W
authors.initials: DW
authors.lastname: Self
authors.forename: Francis S
authors.initials: FS
authors.lastname: Lee
authors.forename: Carol A
authors.initials: CA
authors.lastname: Tamminga
authors.forename: Donald C
authors.initials: DC
authors.lastname: Cooper
authors.forename: Howard K
authors.initials: HK
authors.lastname: Gershenfeld
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nestler
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology*; D003863:Depression / Q000378:metabolism; D004298:Dopamine / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009714:Nucleus Accumbens / Q000378:metabolism; D011110:Polymorphism, Genetic; D012201:Reward; D015398:Signal Transduction; D012919:Social Behavior; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology*; D017557:Ventral Tegmental Area / Q000503:physiopathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004298:Dopamine