The cholinergic REM induction test with RS 86 after scopolamine pretreatment in healthy subjects.
A shortened latency of rapid eye movement (REM) sleep is one of the most stable biological abnormalities described in depressive patients. According to the reciprocal interaction model of non-REM and REM sleep regulation, REM sleep disinhibition at the beginning of the night in depression is a consequence of heightened central nervous system cholinergic transmitter activity in relation to aminergic transmitter activity. A recent study has indicated that muscarinic supersensitivity, rather than quantitatively enhanced cholinergic activity, may be the primary cause of REM sleep abnormalities in depression. The present study tested this hypothesis by treating healthy volunteers for 3 days with a cholinergic antagonist (scopolamine) in the morning, in an effort to induce muscarinic receptor supersensitivity. On the last day of scopolamine administration, RS 86, an orally active cholinergic agonist, was administered before bedtime to test whether this procedure would induce sleep onset REM periods. Whereas scopolamine treatment tended to advance REM sleep and to heighten REM density in healthy controls in comparison to NaCl administration, the additional cholinergic stimulation did not provoke further REM sleep disinhibition. This result underlines the need to take a hypofunction of aminergic transmitter systems into account in attempts to explain the pronounced advance of REM sleep typically seen in depressives.
Riemann
D
D
Sleep-EEG Laboratory, Psychiatric Clinic of the Central Institute of Mental Health, Mannheim, Germany.
Hohagen
F
F
Fleckenstein
P
P
Schredl
M
M
Berger
M
M
D000328:Adult; D000339:Affect / Q000187:drug effects; D000704:Analysis of Variance; D003071:Cognition / Q000187:drug effects; D006801:Humans; D008297:Male; D010277:Parasympathomimetics / Q000008:administration & dosage / Q000494:pharmacology; D010919:Placebos; D011950:Receptors, Cholinergic / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D012601:Scopolamine / Q000008:administration & dosage* / Q000494:pharmacology; D012893:Sleep Wake Disorders / Q000209:etiology*; D012895:Sleep, REM; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D013388:Succinimides / Q000008:administration & dosage / Q000494:pharmacology; D013647:Task Performance and Analysis; D013997:Time Factors
D010277:Parasympathomimetics; D010919:Placebos; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D013388:Succinimides; C001886:2-ethyl-8-methyl-2,8-diazaspiro(4,5)decane-1,3-dione; D012965:Sodium Chloride; D012601:Scopolamine