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Opioids activate G proteins in REM sleep-related brain stem nuclei of rat
M L Capece1, H A Baghdoyan, R Lydic
1Department of Anesthesia, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Abstract:
Mu opioid receptors within the pontine reticular formation contribute to opioid-induced rapid eye movement (REM) sleep inhibition. Mu receptors are coupled to guanine nucleotide binding (G) proteins and this study tested the hypothesis that the micro opioid agonist [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin (DAMGO) would activate G proteins in rat brain stem nuclei known to regulate REM sleep. In vitro autoradiography of DAMGO-stimulated [35S]GTPgammaS binding showed that, compared with basal [35S]GTPgammaS binding, DAMGO significantly increased G protein activation in the nucleus pontis oralis (56.2%), nucleus pontis caudalis (57.3%), laterodorsal tegmental nucleus (75.8%), pedunculopontine tegmental nucleus (72.4%), nucleus locus coeruleus (77.2%) and dorsal raphe nucleus (73.4%). DAMGO stimulation of [35S]GTPgammaS binding in nuclei regulating REM sleep suggests that opioid-induced REM sleep inhibition involves activation of G proteins.
Insights
Opioid drugs inhibit REM sleep by activating G proteins in specific brainstem areas. This study shows that DAMGO, a mu opioid agonist, activates these G proteins in key REM sleep regulatory nuclei.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Mu opioid receptors are implicated in the inhibition of rapid eye movement (REM) sleep.
- These receptors are known to be coupled to guanine nucleotide binding (G) proteins.
Purpose of the Study:
- To investigate whether the mu opioid agonist DAMGO activates G proteins in rat brainstem nuclei that regulate REM sleep.
- To understand the role of G protein activation in opioid-induced REM sleep inhibition.
Main Methods:
- In vitro autoradiography was used to measure [35S]GTPgammaS binding.
- DAMGO was applied to brainstem sections to assess G protein activation in specific nuclei.
Main Results:
- DAMGO significantly increased G protein activation in multiple brainstem nuclei.
- Key areas showing increased activation include the nucleus pontis oralis, nucleus pontis caudalis, laterodorsal tegmental nucleus, pedunculopontine tegmental nucleus, nucleus locus coeruleus, and dorsal raphe nucleus.
Conclusions:
- DAMGO's stimulation of G protein binding in REM sleep-regulating nuclei supports its role in this process.
- Opioid-induced REM sleep inhibition is suggested to involve the activation of G proteins.