Cholinergic and noradrenergic neurotransmission: impact on REM sleep regulation in healthy subjects and depressed patients.

The reciprocal interaction model of NonREM- and REM sleep regulation suggests that the cycling alternating pattern of Non-REM- and REM sleep is under the control of noradrenergic/serotonergic and cholinergic neuronal networks. This model was tested in healthy humans by administration of cholinergic agonists/antagonists and noradrenergic antagonists prior to or during sleep. Cholinomimetics like physostigmine, RS 86 and galanthamine provoked an earlier onset of REM sleep, whereas subchronic treatment with scopolamine, a cholinergic antagonist, only led to a heightening of REM density. Simultaneous administration of noradrenergic antagonists with a cholinergic agonist did not provoke a more pronounced REM sleep advance. Comparative studies with the cholinergic agonist RS 86 in depressed patients, schizophrenic patients and patients with other psychiatric disorders revealed the most pronounced REM sleep response in the depressed group. The REM sleep response to cholinergic stimulation in depression did however not predict the treatment response to a differential-therapeutic strategy.