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Updated: May 11, 2026

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Restraint to Induce Stress in Mice and Rats
Published on: December 6, 2024
Prefrontal/amygdalar system determines stress coping behavior through 5-HT/GABA connection
Diego Andolina1, Dario Maran, Alessandro Valzania
1Santa Lucia Foundation, Rome, Italy. diego.andolina@gmail.com
Summary
Prefrontal serotonin (5-HT) regulates amygdalar GABA, influencing how mice cope with stress. This pathway is crucial for stress-induced behaviors and determining healthy or pathogenic outcomes.
Area of Science:
- Neuroscience
- Behavioral Science
- Stress Research
Background:
- Coping mechanisms are essential for managing stressful situations, with outcomes ranging from healthy to pathogenic.
- The medial prefrontal cortex (mpFC) and amygdala are key brain regions involved in stress-related behaviors.
- mpFC regulates amygdala arousal, and prefrontal serotonin (5-HT) and amygdalar GABA play critical roles in this circuitry.
Purpose of the Study:
- To investigate if amygdalar GABA regulation by prefrontal 5-HT is involved in processing stressful experiences.
- To determine the role of this pathway in influencing coping outcomes in mice.
Main Methods:
- Selective 5-HT depletion in the mpFC of mice.
- Measurement of GABA release in the basolateral amygdala (BLA) under stress.
- Utilizing the Forced Swimming Test (FST) to assess coping behaviors.
- Employing a prefrontal-amygdala disconnection procedure to disrupt serial connectivity.
Main Results:
- Bilateral 5-HT depletion in mpFC reduced stress-induced GABA release in the BLA and increased passive coping (immobility) in the FST.
- Disrupting prefrontal-amygdalar serial connectivity decreased immobility in the FST.
Conclusions:
- Prefrontal 5-HT and amygdalar GABA transmission are critical for processing stressful experiences.
- The prefrontal/amygdala connectivity mediated by these neurotransmitters is a key neural mechanism underlying stress-induced behaviors and coping outcomes.
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