Differential effect of an anticholinergic antidepressant on sleep-dependent memory consolidation.
OBJECTIVE
Rapid eye movement (REM) sleep is considered critical to the consolidation of procedural memory - the memory of skills and habits. Many antidepressants strongly suppress REM sleep, however, and procedural memory consolidation has been shown to be impaired in depressed patients on antidepressant therapy. As a result, it is important to determine whether antidepressive therapy can lead to amnestic impairment. We thus investigated the effects of the anticholinergic antidepressant amitriptyline on sleep-dependent memory consolidation.


METHODS
Double-blind, placebo-controlled, randomized, parallel-group study.


METHODS
Sleep laboratory.


METHODS
Twenty-five healthy men (mean age: 26.8 ± 5.6 y).


METHODS
75 mg amitriptyline versus placebo.


RESULTS
To test memory consolidation, a visual discrimination task, a finger-tapping task, the Rey-Osterrieth Complex Figure Test, and the Rey Auditory-Verbal Learning Test were performed. Sleep was measured using polysomnography. Our findings show that amitriptyline profoundly suppressed REM sleep and impaired perceptual skill learning, but not motor skill or declarative learning.


CONCLUSIONS
Our study is the first to demonstrate that an antidepressant can affect procedural memory consolidation in healthy subjects. Moreover, considering the results of a recent study, in which selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors were shown not to impair procedural memory consolidation, our findings suggest that procedural memory consolidation is not facilitated by the characteristics of REM sleep captured by visual sleep scoring, but rather by the high cholinergic tone associated with REM sleep. Our study contributes to the understanding of potentially undesirable behavioral effects of amitriptyline.
Department of Physiology (CBF), Charité - Universitätsmedizin Berlin, D-14195 Berlin, Germany ; German Center for Neurodegenerative Diseases (DZNE), D-39120 Magdeburg, Germany ; Department of Psychology, Humboldt-University, D-10099 Berlin, Germany.
Monique
M
Goerke
Department of Physiology (CBF), Charité - Universitätsmedizin Berlin, D-14195 Berlin, Germany ; Department of Psychiatry and Psychotherapy, Georg-August-University, D-37099 Göttingen, Germany ; Department of Psychiatry and Psychotherapy, University of Rostock, D-18147 Rostock, Germany.
Stefan
S
Cohrs
Department of Physiology (CBF), Charité - Universitätsmedizin Berlin, D-14195 Berlin, Germany ; Department of Psychiatry and Psychotherapy, Georg-August-University, D-37099 Göttingen, Germany.
Andrea
A
Rodenbeck
Department of Physiology (CBF), Charité - Universitätsmedizin Berlin, D-14195 Berlin, Germany ; German Heart Institute Berlin, D-13353 Berlin, Germany.
Dieter
D
Kunz
D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000328:Adult; D000639:Amitriptyline / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology; D017286:Polysomnography; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology; D013647:Task Performance and Analysis; D055815:Young Adult
D018759:Adrenergic Uptake Inhibitors; D000929:Antidepressive Agents, Tricyclic; D018680:Cholinergic Antagonists; D000639:Amitriptyline
amitriptyline; anticholinergic drug; antidepressant; memory consolidation; sleep