Muscarinic receptor subtypes in the medial preoptic area and sleep-wake cycles

To clarify which muscarinic receptor subtype(s) mediate changes in sleep and cortical temperature (T-cort) induced by carbachol microinjections into the medial preoptic area (MPA), pirenzepine, tripitramine and +/-p >$($) over bar-fluoro-hexahydro-sila-difenidol (p-F-HHSiD), which are highly selective muscarinic M(1), M(2) and M(3) antagonists, respectively, were microinjected into the MPA of rats. Whereas pirenzepine (3.45 and 7.08 nmol) and p-F-HHSiD (3.90 and 7.80 nmol) were without effect, tripitramine (0.67 and 3.37 nmol) enhanced wakefulness, decreased slow wave and desynchronized sleep, and raised T-cort with the higher dose. The data suggest that in the MPA only M(2) muscarinic subtypes may be functionally important in mediating the cholinergic effects on sleep and thermoregulation.