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.