Induction of wakefulness and inhibition of active (REM) sleep by GABAergic processes in the nucleus pontis oralis.
The present study was undertaken to explore the role of brainstem GABAergic processes in the control of the behavioral states of sleep and wakefulness, and to compare the effects of GABAA agonists and antagonists with those of GABAB agonists and antagonists on these behavioral states. Accordingly, the following drugs were microinjected into the nucleus pontis oralis (NPO) in chronic, unanesthetized cats: muscimol (GABAA agonist), bicuculline (GABAA antagonist), baclofen (GABAB agonist) and phaclofen (GABAB antagonist). The percentage, latency, frequency and duration of each behavioral state were measured in order to quantify the effects of these microinjections on wakefulness and sleep. Microinjections of either muscimol or baclofen immediately induced wakefulness. There was a significant increase in the duration and the percentage of time spent in wakefulness as well as an increase in the latency to active (REM) sleep. These changes were accompanied by a decrease in the percentage of time spent in active and quiet sleep. In contrast, injections of bicuculline or phaclofen produced active sleep. The percentage of time spent in active sleep and the frequency of active sleep increased while the percentage of time spent in wakefulness and the latency to active sleep was significantly reduced. The effects of GABAA receptor agonists and antagonists on wakefulness and active sleep were comparable, but stronger than those of GABAB receptor agonists and antagonists. These data indicate that pontine GABAergic processes acting on both GABAA and GABAB receptors play a critical role in generating and maintaining wakefulness and in controlling the occurrence of state of active sleep.
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Department of Physiology, Brain Research Institute, School of Medicine, University of California, Los Angeles, CA 90095, USA.
Morales
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D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives* / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002415:Cats; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009118:Muscimol / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D011149:Pons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011963:Receptors, GABA-A / Q000378:metabolism; D012154:Reticular Formation / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology*; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D011963:Receptors, GABA-A; C052329:phaclofen; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D001640:Bicuculline