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Endocannabinoid interference blocks post-global cerebral ischemia depression through prefrontal cortico-amygdala
Zhaoyuan Tu1,2, Yao Ma1,2, Huiping Shang3
1Mental Health Center, West China Hospital of Sichuan University, Chengdu, China.
Summary
Post-global cerebral ischemia depression (PGCID) is a common condition. Targeting cannabinoid type-1 receptor (CB1R) signaling in specific brain circuits offers a potential treatment for PGCID.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Transient global cerebral ischemia (GCI) affects many cardiac arrest survivors.
- Up to 45% of GCI survivors develop post-global cerebral ischemia depression (PGCID).
- Current clinical treatments for PGCID are unknown.
Purpose of the Study:
- To investigate the mechanisms underlying PGCID.
- To identify potential therapeutic targets for PGCID.
Main Methods:
- Utilized a mouse model of GCI and acute stress.
- Administered cannabinoid type-1 receptor (CB1R) antagonists and inhibitors of endocannabinoid (eCB) synthesis.
- Performed optogenetic activation of vmPFC-BLA projections.
- Analyzed mRNA expression of eCB synthesis and degradation enzymes.
Main Results:
- CB1R antagonists, CB1R knockout, and eCB synthesis inhibition blocked stress-induced PGCID.
- Acute stress increased CB1R activity in vmPFC-BLA projections, indicating a role for eCB signaling.
- Optogenetic activation of vmPFC-BLA CB1Rs induced PGCID-like behaviors.
- Decreased eCB degradation in vmPFCs of GCI mice was observed.
Conclusions:
- Reduced eCB degradation and increased eCB signaling in vmPFC-BLA circuits contribute to PGCID.
- Interfering with eCB signaling systemically or within vmPFC-BLA circuits may treat PGCID.
