Citation

Adachi M, Autry AE, Mahgoub M, Suzuki K, Monteggia LM. Neuropsychopharmacology 2016; 42(4): 886-894.

Affiliation

Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX.

Copyright

(Copyright © 2016, Nature Publishing Group)

DOI

10.1038/npp.2016.201

PMID

27634357

Abstract

Brain-derived neurotrophic factor (BDNF) and its high affinity receptor, tropomyosin receptor kinase B (TrkB), play important roles in neural plasticity and are required for antidepressant efficacy. Studies examining the role of BDNF-TrkB signaling in depression and antidepressant efficacy have largely focused on the limbic system leaving it unclear whether this signaling is important in other brain regions. BDNF and TrkB are both highly expressed in the dorsal raphe nucleus (DRN), a brain region that has been suggested to play a role in depression and antidepressant action, although it is unknown whether BDNF and TrkB in the dorsal raphe nucleus are involved in these processes. We combined the adeno-associated virus (AAV) with the Cre-loxP site specific recombination system to selectively knockdown either Bdnf or TrkB in the dorsal raphe nucleus. These mice were then characterized in several behavioral paradigms including measures of depression-related behavior and antidepressant efficacy. We show that knockdown of TrkB, but not Bdnf, in the dorsal raphe nucleus results in loss of antidepressant efficacy and increased aggression-related behavior. We also show that knockdown of TrkB, or Bdnf, in this brain region does not impact weight, activity levels, anxiety, or depression-related behaviors. These data reveal a critical role for TrkB signaling in the dorsal raphe nucleus in mediating antidepressant responses and normal aggression behavior. The results also suggest a non-cell autonomous role for BDNF in the dorsal raphe nucleus in mediating antidepressant efficacy.Neuropsychopharmacology accepted article preview online, 16 September 2016. doi:10.1038/npp.2016.201.

Language: en