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Updated: Jun 27, 2025

Using Chronic Social Stress to Model Postpartum Depression in Lactating Rodents
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Increasing CB2 Receptor Activity after Early Life Stress Prevents Depressive Behavior in Female Rats.

Susan L Andersen1

  • 1Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Biomolecules
|April 27, 2024
PubMed
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Juvenile exposure to methylphenidate and guanfacine in rats: effects on early delay discounting and later cocaine-taking behavior.

Psychopharmacologyยท2018
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Early life adversity in female rats can lead to depression by altering cannabinoid receptor 2 (CB2) expression in the brain. Boosting CB2 levels in the prelimbic cortex may prevent depressive behaviors.

Area of Science:

  • Neuroscience
  • Psychiatry
  • Pharmacology

Background:

  • Early life adversity is linked to depression, parvalbumin interneuron loss, and neuroinflammation.
  • Individuals with maltreatment history may self-medicate with cannabis earlier in life.
  • Cannabinoid receptor 2 (CB2) possesses anti-inflammatory properties relevant to neurological conditions.

Purpose of the Study:

  • To investigate the impact of maternal separation (MS) on cannabinoid receptor 2 (CB2) expression in the female rat prelimbic cortex.
  • To determine the role of CB2 in depressive-like behaviors following early life adversity.
  • To explore therapeutic potential of modulating CB2 for depression.

Main Methods:

  • Maternal separation (MS) model in female rats to simulate early adversity.
Keywords:
CB2PVadversitydepressionfemaleinflammationmicrogliastress

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  • Western immunoblots to assess MARCH7 and NLRP3 levels.
  • Immunohistochemistry and stereology to quantify parvalbumin-immunoreactive cells and CB2 receptor expression.
  • Confocal and triple-label microscopy to examine CB2 colocalization with microglia and parvalbumin neurons.
  • Behavioral tests to assess depressive-like behaviors.
  • Pharmacological (HU-308 agonist) and viral vector interventions targeting CB2 in the prelimbic cortex.

    • Main Results:

    • MS females showed reduced MARCH7 and increased NLRP3 in the prelimbic cortex.
    • CB2 receptor expression initially increased at postnatal day 25 (P25) and decreased by P40 in MS females, with no change in controls.
    • CB2 receptors were localized to microglia surrounding parvalbumin neurons.
    • Depressive-like behaviors were elevated in MS animals at P40.
    • Treatment with a CB2 agonist or lentiviral CB2 overexpression in the prelimbic cortex reduced depressive-like behaviors in MS rats.

    Conclusions:

    • Early life adversity alters CB2 receptor expression dynamics in the female rat prelimbic cortex.
    • CB2 receptor expression in the prelimbic cortex is critical for preventing depressive behavior in the context of early adversity.
    • Modulating CB2 expression presents a potential therapeutic strategy for depression linked to early life stress.