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Polygraphic Recording Procedure for Measuring Sleep in Mice
Published on: January 25, 2016
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Trace Amine-Associated Receptor 1 Agonists as Narcolepsy Therapeutics
Sarah W Black1, Michael D Schwartz2, Tsui-Ming Chen1
1Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, California.
Biological Psychiatry
|December 7, 2016
Summary
Trace amine-associated receptor 1 (TAAR1) agonists show promise for treating narcolepsy. These compounds reduced cataplexy and suppressed rapid eye movement (REM) sleep in mouse models, suggesting a new therapeutic avenue.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Narcolepsy is a REM sleep disorder causing excessive daytime sleepiness and cataplexy.
- Current narcolepsy treatments have abuse potential or side effects.
- Trace amine-associated receptor 1 (TAAR1) agonists promote wakefulness.
Purpose of the Study:
- To evaluate the efficacy of TAAR1 agonism in mouse models of narcolepsy.
- To investigate the effects of TAAR1 agonists on sleep/wake parameters and cataplexy.
Main Methods:
- Two mouse models of narcolepsy were used.
- Mice underwent surgical implantation for physiological monitoring.
- TAAR1 agonists (RO5256390 and RO5263397) were administered to assess effects on sleep, activity, temperature, and cataplexy.
Main Results:
- TAAR1 agonists reduced REM sleep and suppressed non-REM sleep, promoting wakefulness.
- Both tested TAAR1 agonists mitigated cataplexy in narcolepsy models.
- Therapeutic benefits were linked to reduced cataplexy episodes and duration.
Conclusions:
- TAAR1 agonism presents a novel therapeutic strategy for narcolepsy.
- Suppression of REM sleep may be the underlying mechanism.
- This research offers a potential new treatment for this orphan disease.
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