Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions.
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.
Krishnan
Vaishnav
V
Department of Psychiatry, The University of Texas Southwestern Medical Center (UTSWMC), 5323 Harry Hines Boulevard, Dallas, TX 75390-9070, USA.
Han
Ming-Hu
MH
Graham
Danielle L
DL
Berton
Olivier
O
Renthal
William
W
Russo
Scott J
SJ
Laplant
Quincey
Q
Graham
Ami
A
Lutter
Michael
M
Lagace
Diane C
DC
Ghose
Subroto
S
Reister
Robin
R
Tannous
Paul
P
Green
Thomas A
TA
Neve
Rachael L
RL
Chakravarty
Sumana
S
Kumar
Arvind
A
Eisch
Amelia J
AJ
Self
David W
DW
Lee
Francis S
FS
Tamminga
Carol A
CA
Cooper
Donald C
DC
Gershenfeld
Howard K
HK
Nestler
Eric J
EJ
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
D019208:Brain-Derived Neurotrophic Factor; D004298:Dopamine