Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress.
Mice experiencing repeated aggression develop a long-lasting aversion to social contact, which can be normalized by chronic, but not acute, administration of antidepressant. Using viral-mediated, mesolimbic dopamine pathway-specific knockdown of brain-derived neurotrophic factor (BDNF), we showed that BDNF is required for the development of this experience-dependent social aversion. Gene profiling in the nucleus accumbens indicates that local knockdown of BDNF obliterates most of the effects of repeated aggression on gene expression within this circuit, with similar effects being produced by chronic treatment with antidepressant. These results establish an essential role for BDNF in mediating long-term neural and behavioral plasticity in response to aversive social experiences.
Berton
Olivier
O
Department of Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9070, USA.
McClung
Colleen A
CA
Dileone
Ralph J
RJ
Krishnan
Vaishnav
V
Renthal
William
W
Russo
Scott J
SJ
Graham
Danielle
D
Tsankova
Nadia M
NM
Bolanos
Carlos A
CA
Rios
Maribel
M
Monteggia
Lisa M
LM
Self
David W
DW
Nestler
Eric J
EJ
D000374:Aggression; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology*; D003863:Depression / Q000503:physiopathology; D004291:Dominance-Subordination; D004298:Dopamine / Q000502:physiology*; D005473:Fluoxetine / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D007099:Imipramine / Q000494:pharmacology; D008032:Limbic System / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology; D009714:Nucleus Accumbens / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D012919:Social Behavior; D012934:Social Isolation; D013315:Stress, Psychological; D017557:Ventral Tegmental Area / Q000378:metabolism
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D016760:Proto-Oncogene Proteins c-fos; D005473:Fluoxetine; D007099:Imipramine; D004298:Dopamine