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Polygraphic Recording Procedure for Measuring Sleep in Mice
Published on: January 25, 2016
The selective group mGlu2/3 receptor agonist LY379268 suppresses REM sleep and fast EEG in the rat
I Feinberg1, I G Campbell, D D Schoepp
1Department of Psychiatry, University of California at Davis, Davis, CA 95616, USA. ifeinberg@ucdavis.edu
Abstract:
Studies of ionotropic receptors indicate that glutamate (Glu) neurotransmission plays a role in sleep. Here, we show for the first time that metabotropic 2/3 Glu (mGlu2/3) receptors play an active or permissive role in the control of REM sleep. The potent, selective, and systemically active mGlu2/3 receptor agonist LY379268 was administered systemically in doses of 1.0 and 0.25 mg/kg sc. The drug produced a dose-dependent suppression of rapid eye movement (REM) sleep and fast (10-50 Hz) EEG in non-rapid eye movement (NREM) sleep. The 1.0-mg/kg effect on REM sleep was remarkably powerful: REM sleep was totally suppressed in the 6-h postinjection and reduced by 80% in the next 6 h. NREM duration was unchanged during the REM suppression in spite of the strong and unusual depression of EEG power in fast NREM frequencies. These sleep and EEG effects were unaccompanied by motor or behavioral abnormalities. We hypothesize that the REM and the fast EEG suppression were both caused by a depression of brain arousal levels by LY379268. If correct, depressing arousal by reducing excitatory neurotransmission with an mGlu2/3 receptor agonist produces electrophysiological effects that differ drastically from those produced by depressing arousal by enhancing neural inhibition with GABAergic drugs. This different approach to modifying the excitation/inhibition balance in the brain might yield novel therapeutic actions.
Insights
Metabotropic 2/3 glutamate (mGlu2/3) receptors actively control REM sleep. A selective agonist, LY379268, dose-dependently suppressed REM sleep and fast EEG activity in NREM sleep without motor side effects.
Area of Science:
- Neuroscience
- Sleep Science
- Pharmacology
Background:
- Glutamate (Glu) neurotransmission is implicated in sleep regulation.
- Ionotropic glutamate receptors' role in sleep is established.
- The specific role of metabotropic 2/3 Glu (mGlu2/3) receptors in sleep remains unclear.
Purpose of the Study:
- To investigate the role of mGlu2/3 receptors in the control of REM sleep.
- To determine the effects of a selective mGlu2/3 receptor agonist on sleep architecture and EEG activity.
Main Methods:
- Systemic administration of the mGlu2/3 receptor agonist LY379268 (1.0 and 0.25 mg/kg) in rats.
- Monitoring of sleep patterns, including REM and NREM sleep duration.
- Analysis of electroencephalogram (EEG) power in different frequency bands during NREM sleep.
Main Results:
- LY379268 produced a dose-dependent suppression of REM sleep.
- A high dose (1.0 mg/kg) nearly abolished REM sleep for 12 hours post-injection.
- Fast EEG frequencies (10-50 Hz) during NREM sleep were significantly reduced, without altering NREM duration.
- No motor or behavioral abnormalities were observed.
Conclusions:
- mGlu2/3 receptors play an active or permissive role in regulating REM sleep.
- Suppression of REM sleep and fast EEG activity by LY379268 may be due to reduced brain arousal levels.
- Modulating brain excitation/inhibition balance via mGlu2/3 agonism offers a distinct approach compared to GABAergic drugs, potentially yielding novel therapeutics.
