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Published on: November 11, 2022
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A Key Role for Neurotensin in Chronic-Stress-Induced Anxiety-Like Behavior in Rats.
Catherine P Normandeau1,2, Ana Paula Ventura-Silva3,4, Emily R Hawken1,2
1Center for Neuroscience Studies, Queen's University, Kingston, ON, Canada.
Summary
Chronic stress increases anxiety by altering neuropeptide signaling in the brain. Neurotensin (NT) plays a key role in stress-induced anxiety-like behaviors, offering a potential therapeutic target.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
- Molecular Psychiatry
Background:
- Chronic stress is a primary driver of anxiety disorders.
- Neuropeptides are implicated in stress and anxiety, but their precise roles remain unclear.
- The bed nucleus of the stria terminalis (BNST) is a key brain region involved in anxiety disorders.
Purpose of the Study:
- To investigate the role of neuropeptides in modulating synaptic transmission in the BNST in a rat model of chronic stress.
- To determine how chronic unpredictable stress (CUS) alters neuropeptide function in the oval BNST (ovBNST).
- To explore neurotensin (NT) as a potential therapeutic target for stress-induced anxiety.
Main Methods:
- Utilized a rat model of chronic unpredictable stress (CUS) to induce anxiety-like behaviors.
- Employed brain slice neurophysiology to examine synaptic transmission in the ovBNST.
- Used behavioral pharmacology, specifically blocking neurotensin receptors, to assess anxiety-like behaviors in the elevated plus maze.
Main Results:
- In non-stressed rats, neurotensin (NT) and corticotropin-releasing factor (CRF) co-acted to enhance inhibitory synaptic transmission in the ovBNST.
- Chronic unpredictable stress (CUS) potentiated this effect, with an increased contribution from NT over CRF.
- Opioid neuropeptides consistently reduced excitatory synaptic transmission in the ovBNST, irrespective of stress.
- Blocking NT receptors in the ovBNST completely eliminated stress-induced anxiety-like behaviors.
Conclusions:
- Chronic stress alters neuropeptide modulation of synaptic transmission in the BNST, particularly enhancing the role of neurotensin.
- Neurotensin signaling in the ovBNST is critical for stress-induced anxiety-like behaviors, specifically exaggerated avoidance.
- Neurotensin represents a promising therapeutic target for anxiety disorders stemming from chronic stress.

