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Updated: May 15, 2026
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Trace Fear Conditioning in Mice
Published on: March 20, 2014
Caloric restriction enhances fear extinction learning in mice
Megan C Riddle1, Morgan C McKenna, Yone J Yoon
1Weill Cornell/Rockefeller/Sloan Kettering Tri-Insitutional MD-PhD Program, Weill Cornell Medical College, New York, NY 10065, USA.
Summary
Caloric restriction (CR) enhances fear extinction learning and memory retention in mice through a serotonin transporter (SERT)-dependent pathway. This suggests CR may help manage anxiety disorders by improving the brain's ability to reassess danger cues.
Area of Science:
- Neuroscience
- Behavioral Science
- Psychiatry
Background:
- Fear extinction learning is crucial for managing anxiety disorders but is often impaired.
- Selective serotonin reuptake inhibitors (SSRIs) improve fear extinction and have anxiolytic effects.
- Caloric restriction (CR) exhibits SSRI-like effects on neural plasticity and anxiety-related behaviors.
Purpose of the Study:
- To investigate the effects of CR on fear extinction learning and retention in mice.
- To determine if CR's effects on fear extinction are dependent on the serotonin transporter (SERT).
Main Methods:
- Wild type and SERT knockout mice underwent 7-day CR with significant weight loss.
- Mice were assessed for cued fear learning and anxiety-related behaviors.
- Behavioral and molecular effects were compared between CR, fluoxetine treatment, and combined treatments.
Main Results:
- CR significantly enhanced fear extinction learning and its retention in adolescent female mice and adult mice of both sexes.
- These CR-induced enhancements were absent in SERT knockout mice.
- CR mimicked the effects of fluoxetine, with no additive benefits when combined.
Conclusions:
- Caloric restriction enhances fear extinction learning via a SERT-dependent mechanism.
- CR's effects are comparable to SSRI treatment, suggesting a shared pathway.
- Findings may inform understanding of anxiety in eating disorders like anorexia nervosa, where CR might serve to mitigate fear responses.
