Differential effects of M2 and M3 muscarinic antagonists on the sleep-wake cycle.
To study the role of muscarinic receptor subtypes in sleep control, methoctramine (25, 50, 75 micrograms), a highly selective M2 antagonist, was injected intra-cerebroventricularly into freely moving rats. Methoctramine induced a dose-dependent increase in desynchronized sleep (DS) latency (from 62.7 +/- 10 min following saline to 122.4 +/- 13.8 min with the lowest dose) and a 75% decrease in the amount of DS in 6 h recordings. 4DAMP (a M3/M1 selective antagonist) did not significantly change DS latency and percentage time, but it reduced wakefulness (from 38 +/- 2.8% following saline to 25.3 +/- 3.7% with a dose of 2.5), and increased slow wave sleep. The results suggest that M2 muscarinic receptors play a selective role in DS physiology.
Imeri
L
L
Istituto di Fisiologia Umana II, Università degli Studi, Milano, Italy.
Bianchi
S
S
Angeli
P
P
Mancia
M
M
D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003959:Diamines / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012890:Sleep / Q000187:drug effects*; D013565:Sympatholytics / Q000494:pharmacology*; D014851:Wakefulness / Q000187:drug effects*
D003959:Diamines; D010880:Piperidines; D011976:Receptors, Muscarinic; D013565:Sympatholytics; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; C054938:methoctramine