33 The REM-promoting system comprises “REM-on” cholinergic neurons located in the laterodorsal

tegmental (LDT) and pediculopontine tegmental (PPT) nuclei (Figure 3). The McCarley and Hobson reciprocal interaction model, first proposed in 1975, and regularly revisited,14 posits a bidirectional inhibitory influence between these REM-on neurons and both the serotonergic Inhibitors,research,lifescience,medical DRN and the noradrenergic LC, called “REM-off” neurons. Transition from NREM to REM occurs when activity in the aminergic REM-off neurons ceases. Cholinergic LDT/PPT REM-on neurons are then Compound C purchase involved in the initiation of cortical desynchronization through excitatory inputs to the thalamus and in the occurrence of muscle atonia and REMs. During Inhibitors,research,lifescience,medical REM sleep, the excitatory input from the REM-on neurons to the DRN and LC leads to a gradual increase in the activity of the REMoff neurons, which in turn inhibit REM-on neurons until the REM episode ends. GABAergic and glutamatergic modulations of this aminergic-cholinergic interplay have been proposed in the revised version of the model.14 Figure 3 Inhibitors,research,lifescience,medical Simplified representation of various structures implicated in rapid

eye movement (REM) mechanisms and their interrelationships. Light-blue boxes, activated structures; blue boxes, deactivated structures; light-blue arrows, excitatory influences; blue … The effects of drugs on wake-and sleep-inducing mechanisms In the following sections, we will review the effects of

psychotropic drugs on the three interacting Inhibitors,research,lifescience,medical neuronal systems that have been proposed to play a key role in sleep-wake regulation (the wake-promoting system, the NREM-promoting system, and the REM-promoting system). The first four sections deal with drugs acting on wake- or NREM sleep-promoting neurons, while the following section concerns drugs acting on the REMpromoting system with special reference to antidepressant drugs. Whether drugs induce wakefulness (“waking drugs”) or sleep (“hypnosedative drugs”) depend on their liability to stimulate or inhibit wake- or NREM sleep-promoting neurons. Before going further, it Inhibitors,research,lifescience,medical should be stressed that the net effects of a hypnosedative drug inhibiting wake-promoting neurons will be very similar to the effects of a drug stimulating NREM-promoting also neurons. The converse is true for waking drugs: the effects of a drug inhibiting NREM-promoting neurons will parallel those induced by a drug stimulating wakepromoting neurons. Finally, it should be recognized that a distinction between drugs acting on wake- or NREMpromoting neurons is somewhat arbitrary, due to the close reciprocal negative feedback existing between these two groups of neurons.7 Some drugs directly influence both wake-promoting neurons and sleep-promoting neurons, but in an opposite way; this is the case for compounds influencing adenosine transmission such as caffeine.