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 M(1), M(2) and M(3) antagonists, respectively, were dissolved in 0.1 mu l of sterile isotonic saline (0.2 mu l of distilled water for p-F-HHSiD) and injected into the pontine reticular nucleus, where the administration of 0.5 mu g 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 M(2) 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 M(1) or M(2) antagonists. The results support the hypothesis that at the brain stem level only M(2) receptors are involved in sleep mechanisms and, particularly, in the generation and maintenance of DS.