Social brain
Does turning down orexin make stressed rats resilient?
Open access · cc by · source: Europe PMC
Rats that actively coped with social defeat had lower prepro-orexin mRNA; inhibiting lateral-hypothalamic orexin neurons with DREADDs on days 6–8 boosted social interaction and reduced forced-swim immobility in previously passive, vulnerable rats.
Study at a glance
- Design
- Animal / in-vitro — Rat resident-intruder social defeat with in situ/qPCR of prepro-orexin, then orexin-targeted hM4Di DREADDs + CNO on days 6–8
- N
- N=12 · Key in situ after DREADDs+behavior n=12/group; several ANOVAs n=6/group; phenotypes split by defeat latency over 5–7 days
- Population
- Male rats classified as passive vs active copers during repeated social defeat by Long-Evans residents (plus non-defeated controls)
- Outcome
- Prepro-orexin mRNA; social interaction; forced-swim immobility after inhibiting orexin neurons
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Key findings
Active copers expressed significantly less prepro-orexin mRNA than passive copers. CNO inhibition increased social interaction and decreased depressive-like behavior in the vulnerable group, bringing passive copers toward active-coper interaction times. After FST, CNO lowered prepro-orexin (F(1,38)=8.0, p=0.007).
Methodology
Used 5–7 days of resident-intruder defeat to split passive (<300 s latency) vs active copers, measured lateral-hypothalamic prepro-orexin by in situ/qPCR, then expressed hM4Di in orexin neurons and injected CNO (2 mg/kg) before defeats on days 6–8, followed by social interaction and a 2-day Porsolt FST.
Limitations
Male-rat DREADDs at 2 mg/kg CNO do not prove orexin antagonists treat human PTSD/depression; effects were phenotype-specific and not a general activity increase.
How this study connects
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