TrkB Signaling in Dorsal Raphe Nucleus is Essential for Antidepressant Efficacy and Normal Aggression Behavior

Megumi Adachi, Anita E. Autry-Dixon, Melissa Mahgoub, Kanzo Suzuki, Lisa M. Monteggia

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Brain-derived neurotrophic factor (BDNF) and its high affinity receptor, tropomyosin receptor kinase B (TrkB), have 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 have 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 knock down either Bdnf or TrkB in the DRN. 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 DRN 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 have an impact on weight, activity levels, anxiety, or depression-related behaviors. These data reveal a critical role for TrkB signaling in the DRN in mediating antidepressant responses and normal aggression behavior. The results also suggest a non-cell autonomous role for BDNF in the DRN in mediating antidepressant efficacy.

Original languageEnglish (US)
Pages (from-to)886-894
Number of pages9
JournalNeuropsychopharmacology
Volume42
Issue number4
DOIs
StatePublished - Mar 1 2017
Externally publishedYes

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Aggression
Antidepressive Agents
trkB Receptor
Depression
Brain-Derived Neurotrophic Factor
Brain
Dependovirus
Limbic System
Neuronal Plasticity
tropomyosin kinase
Dorsal Raphe Nucleus
Genetic Recombination
Anxiety
Weights and Measures

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

TrkB Signaling in Dorsal Raphe Nucleus is Essential for Antidepressant Efficacy and Normal Aggression Behavior. / Adachi, Megumi; Autry-Dixon, Anita E.; Mahgoub, Melissa; Suzuki, Kanzo; Monteggia, Lisa M.

In: Neuropsychopharmacology, Vol. 42, No. 4, 01.03.2017, p. 886-894.

Research output: Contribution to journalArticle

Adachi, Megumi ; Autry-Dixon, Anita E. ; Mahgoub, Melissa ; Suzuki, Kanzo ; Monteggia, Lisa M. / TrkB Signaling in Dorsal Raphe Nucleus is Essential for Antidepressant Efficacy and Normal Aggression Behavior. In: Neuropsychopharmacology. 2017 ; Vol. 42, No. 4. pp. 886-894.
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