Activation of signaling pathways downstream of the brain-derived neurotrophic factor receptor, TrkB, in the rat brain by vagal nerve stimulation and antidepressant drugs

Flavia Regina Carreno, Alan Frazer

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Vagal nerve stimulation (VNS) has been approved for treatment resistant depression (TRD) by the Food and Drug Administration (FDA) since 2005. However, the cellular and molecular targets responsible for its effects are still not characterized. Previously, chronic administration of VNS to rats was found to phosphorylate tyrosine 515 on TrkB, the neurotrophin receptor, whereas traditional antidepressants did not do this. In the present study, Western blot analysis was used to characterize activation due to phosphorylation in the hippocampus of down-stream pathways linked to specific key tyrosine residues on TrkB (namely Y816 and Y515) after either acute or chronic administration of VNS and traditional antidepressant drugs. Chronic administration of VNS caused phosphorylation of effectors linked to Y 515; namely Akt, ERK and p70S6 kinase, but this was not produced by either desipramine or sertraline. All the treatments, when given chronically, caused phosphorylation of the transcription factor, CREB. Acute administration of all the treatments also caused phosphorylation of PLCγ1 but this was not maintained with chronic treatment. Further research is required to determine what role, if any, activation of down-stream targets of Y515 plays in the behavioural effects of VNS.

Original languageEnglish (US)
Pages (from-to)247-258
Number of pages12
JournalInternational Journal of Neuropsychopharmacology
Volume17
Issue number2
DOIs
StatePublished - Feb 2014
Externally publishedYes

Fingerprint

trkB Receptor
Vagus Nerve Stimulation
Antidepressive Agents
Phosphorylation
Brain
Tyrosine
Treatment-Resistant Depressive Disorder
Nerve Growth Factor Receptors
Sertraline
Desipramine
United States Food and Drug Administration
Hippocampus
Transcription Factors
Phosphotransferases
Therapeutics
Western Blotting
Research

Keywords

  • Antidepressants
  • desipramine
  • sertraline
  • TrkB
  • vagal nerve stimulation

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Psychiatry and Mental health

Cite this

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