Muramyl dipeptide, amphetamine, and physostigmine: effects on sleep of rabbits.

Muramyl peptides (MPs) are constituents of bacterial cell walls and mammalian tissue. Some MPs have the capacity to enhance slow-wave sleep (SWS). In rabbits, it was unknown whether MPs enhanced SWS by prolonging SWS episodes or by increasing the number of SWS episodes. In rabbits, there is a frequent alternation between sleep and waking; thus, demonstration of induction of new SWS episodes is difficult unless pharmacologic manipulations are used. We injected amphetamine subcutaneously to reduce duration of sleep (from about 45% to 20%) for a period of two hours; it reduced the number of SWS episodes. Muramyl dipeptide (MDP: NAM-L-ala-D-isogln) injected into a lateral ventricle one hour before amphetamine significantly increased the number of SWS episodes. Physostigmine, a cholinergic agonist, was also used. By itself, physostigmine greatly reduced SWS and rapid eye movement sleep. Pretreatment of animals with MDP two hours before physostigmine injection failed to reverse subsequent physostigmine-induced wakefulness. We conclude that MDP has the ability to induce SWS episodes but does not act directly on the thalamocortical cholinergic mechanisms of EEG phenomena. Our results, together with earlier evidence on anatomical levels of action of amphetamine and physostigmine, suggest that the somnogenic mechanisms of MPs likely involve the midbrain.