Selective blockade of different brain stem muscarinic receptor subtypes: effects on the sleep-wake cycle.
Changes induced in the sleep-wake cycle by pontine microinjections of muscarinic antagonists were studied in freely moving rats, instrumented for chronic polygraphic recordings. Pirenzepine (PIR), methoctramine (MET) and p-fluoro-hexahydro-siladifenidol (p-F-HHSiD), which are highly selective M1, M2 and M3 antagonists, respectively, were dissolved in 0.1 microliter of sterile isotonic saline (0.2 microliter of distilled water for p-F-HHSiD) and injected into the pontine reticular nucleus, where the administration of 0.5 microgram carbachol (a mixed muscarinic agonist) induced a 52% increase in the amount of desynchronized sleep (DS) over a 6 h recording period. The blockade of M2 receptors was shown to (i) antagonize DS, by increasing its latency and decreasing its percentage, (ii) decrease slow wave sleep, and (iii) enhance wakefulness. These effects were dose-dependent. No changes in the sleep-wake cycle were observed following microinjection of M1 or M3 antagonists. The results support the hypothesis that at the brain stem level only M2 receptors are involved in sleep mechanisms and, particularly, in the generation and maintenance of DS.
Imeri
L
L
Istituto di Fisiologia Umana II, Università degli Studi, Milano, Italy.
Bianchi
S
S
Angeli
P
P
Mancia
M
M
D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology; D003959:Diamines / Q000008:administration & dosage / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects; D008297:Male; D008845:Microinjections; D018727:Muscarinic Antagonists; D010276:Parasympatholytics / Q000008:administration & dosage / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D010890:Pirenzepine / Q000008:administration & dosage / Q000494:pharmacology; D017286:Polysomnography; D051381:Rats; D012154:Reticular Formation / Q000187:drug effects / Q000502:physiology; D012890:Sleep / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects*
D003959:Diamines; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D010880:Piperidines; C058297:4-fluorohexahydrosiladifenidol; D010890:Pirenzepine; D002217:Carbachol; C054938:methoctramine