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Updated: Mar 10, 2026

Observational Fear as a Model of Affective Empathy in Mice
Published on: November 22, 2024
Increased anxiety but normal fear and safety learning in orexin-deficient mice
1Institute for Pharmacology and Toxicology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
Abstract:
The loss of orexin neurons in humans leads to the disease narcolepsy, characterized by daytime sleepiness and cataplexy. Recent data suggest that orexin is also involved in emotional processing. The goal of the present study was to evaluate fear and safety learning as well as unconditioned fear (anxiety) in orexin-deficient animals. Orexin-deficient mice are an established animal model used to investigate the neuropathology and potential treatments for narcolepsy. Here, we present novel data showing that orexin-deficient mice express increased anxiety in the open field, light-dark box test and carnivore odor-induced avoidance, but are normal in fear and safety learning. These findings suggest an important role of orexin in brain areas involved in anxiety.
Insights
Orexin deficiency in mice increases anxiety behaviors but does not affect fear or safety learning. This suggests orexin plays a key role in regulating anxiety responses.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
Background:
- Orexin neuron loss causes narcolepsy in humans, characterized by sleepiness and cataplexy.
- Emerging evidence indicates orexin's involvement in emotional processing.
Purpose of the Study:
- To investigate the role of orexin in fear and safety learning and unconditioned fear (anxiety).
- To utilize orexin-deficient mice as a model for narcolepsy research.
Main Methods:
- Orexin-deficient mice were assessed for anxiety using behavioral tests: open field, light-dark box, and carnivore odor-induced avoidance.
- Fear and safety learning were evaluated in these mice.
Main Results:
- Orexin-deficient mice exhibited heightened anxiety across multiple tests.
- No significant differences were observed in fear or safety learning between orexin-deficient and control mice.
Conclusions:
- Orexin signaling is crucial for modulating anxiety-like behaviors.
- The findings highlight orexin's specific role in anxiety regulation, distinct from fear and safety learning mechanisms.

