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A role for the extracellular signal-regulated kinase signal pathway in depressive-like behavior

Xiaoli Qi1, Wenjuan Lin, Donglin Wang

  • 1Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Science, 4A Datun Road, Chaoyang District, Beijing 100101, China.

Behavioural Brain Research
|January 23, 2009
PubMed

Insights

The extracellular signal-regulated kinase (ERK) pathway is crucial for regulating mood. Inhibiting ERK in specific brain regions of rats induced depression-like behaviors, suggesting its role in mood disorders.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Psychiatry

Background:

  • The extracellular signal-regulated kinase (ERK) signaling pathway is implicated in cellular processes relevant to mood regulation.
  • Previous research suggests ERK pathway dysfunction in animal models of depression, with normalization upon antidepressant treatment.

Purpose of the Study:

  • To investigate the specific roles of the ERK pathway in the dorsal hippocampus (dHP) and medial prefrontal cortex (mPFC) in depressive-like behaviors.
  • To provide direct evidence for the involvement of the ERK cascade in the pathophysiology of depression.

Main Methods:

  • Rats received daily microinjections of U0126 (an ERK inhibitor) or vehicle into the dHP or mPFC for seven days.
  • Behavioral assessments included the open field test, elevated plus maze, and saccharin preference test.
  • Changes in cyclic AMP-responsive-element-binding protein (CREB) phosphorylation were analyzed.

Main Results:

  • ERK inhibition in the dHP led to anxiety-like behavior and anhedonia.
  • ERK inhibition in the mPFC resulted in anhedonia and impaired locomotion.
  • CREB phosphorylation decreased in both dHP and mPFC following ERK inhibition.

Conclusions:

  • The ERK pathway in both the dHP and mPFC plays a significant role in mediating depressive-like behaviors.
  • These findings highlight the ERK pathway as a potential therapeutic target for depression.

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