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The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice
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Published on: October 24, 2018

Dynorphin, stress, and depression.

Allison T Knoll1, William A Carlezon

  • 1Behavioral Genetics Laboratory, Department of Psychiatry, Harvard Medical School, McLean Hospital, MRC 217, 115 Mill Street, Belmont, MA 02478, USA.

Brain Research
|September 29, 2009
PubMed
Summary
This summary is machine-generated.

Stress activates kappa opioid receptors (KORs), contributing to both acute stress responses and chronic depressive-like behaviors. KOR antagonists may offer therapeutic potential for stress-related disorders by blocking these effects.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Behavioral Science

Background:

  • Stress rapidly triggers hormone and neuropeptide release, including dynorphin, which activates kappa opioid receptors (KORs).
  • KOR signaling in limbic regions can mimic or worsen stress-induced aversive states in animal models.
  • Prolonged KOR activation by chronic stress is linked to depressive-like behaviors and sensitization of stress responses.

Purpose of the Study:

  • To review the role of KOR systems in the acute, delayed, and cumulative effects of stress.
  • To examine behavioral paradigms illustrating stress-KOR interactions across different time scales.
  • To explore the therapeutic potential of KOR antagonists for stress-related conditions.

Main Methods:

  • Literature review focusing on KOR signaling pathways and stress responses.
  • Analysis of behavioral studies in animal models of stress and depression.
  • Consideration of temporal dynamics and mechanisms of KOR-mediated effects.

Main Results:

  • KORs mediate both acute stress adaptations (e.g., analgesia, escape motivation) and chronic prodepressive-like behaviors.
  • KOR signaling contributes to the sensitization of stress-induced behaviors with repeated stress exposure.
  • KOR antagonists effectively block many aversive effects of stress in preclinical models.

Conclusions:

  • KOR systems play a critical role in the multifaceted effects of stress, from acute responses to chronic behavioral changes.
  • KOR antagonists show promise as therapeutics for depression and anxiety disorders by potentially preventing or treating stress-induced behaviors.
  • Further research is needed to elucidate whether KOR antagonists act on the development or expression of stress-induced behaviors.