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Opioid inhibition of rapid eye movement sleep by a specific mu receptor agonist
A Cronin1, J C Keifer, H A Baghdoyan
1Department of Anesthesia, Pennsylvania State University, College of Medicine, Hershey 17033, USA.
Abstract:
Patients receiving opioids report feeling sleepy, but opioids actually inhibit the rapid eye movement phase of sleep (REM). Inhibition of REM sleep is followed by a rebound increase in REM sleep associated with cardiopulmonary complications. The medial pontine reticular formation (mPRF) is a brain region from which morphine can inhibit REM sleep. The present study tested the hypothesis that specific subtypes of opioid receptors within the mPRF mediate inhibition of REM sleep. Synthetic opioid agonists selective for mu, delta and kappa subtypes were microinjected into the mPRF of four awake cats and polygraphic recordings of sleep and breathing were obtained. An enkephalinase inhibitor was microinjected into the mPRF to assess the contribution of endogenous opioids to the control of sleep and breathing. Only the mu agonist significantly inhibited REM sleep, and no opioid depressed breathing. These results demonstrate that opioid-induced REM sleep inhibition is mediated by mu receptor subtypes in the mPRF.
Insights
Opioids inhibit rapid eye movement (REM) sleep by activating mu-opioid receptors in the brainstem
Area of Science:
- Neuroscience
- Sleep Medicine
- Pharmacology
Background:
- Opioid use is associated with sleep disturbances, specifically the inhibition of rapid eye movement (REM) sleep.
- REM sleep suppression can lead to subsequent REM rebound and potential cardiopulmonary complications.
- The medial pontine reticular formation (mPRF) is implicated in morphine's inhibition of REM sleep.
Purpose of the Study:
- To investigate which specific opioid receptor subtypes in the mPRF mediate the inhibition of REM sleep.
- To determine if mu, delta, or kappa opioid receptors are responsible for opioid-induced REM sleep suppression.
Main Methods:
- Microinjection of selective mu, delta, and kappa opioid agonists into the mPRF of awake cats.
- Polygraphic recordings of sleep states and respiratory function were obtained.
- Administration of an enkephalinase inhibitor to assess endogenous opioid involvement.
Main Results:
- Selective mu-opioid receptor agonists significantly inhibited REM sleep.
- Delta and kappa opioid agonists did not affect REM sleep.
- No tested opioid agonists or the enkephalinase inhibitor depressed breathing.
Conclusions:
- Opioid-induced REM sleep inhibition is specifically mediated by mu-opioid receptor subtypes within the mPRF.
- The mPRF is a critical brain region for regulating REM sleep in response to opioids.