Blockade of GABA, type A, receptors in the rat pontine reticular formation induces rapid eye movement sleep that is dependent upon the cholinergic system.
The brainstem reticular formation is an area important to the control of rapid eye movement (REM) sleep. The antagonist of GABA-type A (GABA(A)) receptors, bicuculline methiodide (BMI), injected into the rat nucleus pontis oralis (PnO) of the reticular formation resulted in a long-lasting increase in REM sleep. Thus, one factor controlling REM sleep appears to be the number of functional GABA(A) receptors in the PnO. The long-lasting effect produced by BMI may result from secondary influences on other neurotransmitter systems known to have long-lasting effects. To study this question, rats were surgically prepared for chronic sleep recording and additionally implanted with guide cannulas aimed at sites in the PnO. Multiple, 60 nl, unilateral injections were made either singly or in combination. GABA(A) receptor antagonists, BMI and gabazine (GBZ), produced dose-dependent increases in REM sleep with GBZ being approximately 35 times more potent than BMI. GBZ and the cholinergic agonist, carbachol, produced very similar results, both increasing REM sleep for about 8 h, mainly through increased period frequency, with little reduction in REM latency. Pre-injection of the muscarinic antagonist, atropine, completely blocked the REM sleep-increase by GBZ. GABAergic control of REM sleep in the PnO requires the cholinergic system and may be acting through presynaptic modulation of acetylcholine release.
Marks
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The University of Texas Southwestern Medical Center and Veterans Affairs Medical Center, MC# 151, 4500 South Lancaster Road, Dallas, TX 75216, USA. Gerald.Marks@UTSouthwestern.edu
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D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism*; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D011149:Pons / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012154:Reticular Formation / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018679:Cholinergic Agonists; D018756:GABA Antagonists; D018727:Muscarinic Antagonists; D011724:Pyridazines; D011963:Receptors, GABA-A; C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; D001285:Atropine; D002217:Carbachol; C049853:gabazine; D000109:Acetylcholine; D001640:Bicuculline