Abstract
The mechanisms by which sleep deprivation brings about rapid antidepressant effects
remain to be elucidated. Biological rhythms have the capacity to temporally dissociate
biochemical processes, and imposing a temporal coincidence on normally dissociated
events can have striking and unexpected effects. In this context, it is noteworthy
that the locus coeruleus (LC) noradrenergic projection is quiescent only during rapid-eye-movement
(REM) sleep, when the target tissues display their greatest sensitivity; indeed, the
temporal dissociation between the firing of the LC noradrenergic neurons and the sensitivity
of its postsynaptic targets in the cortex may have considerable relevance for the
antidepressant effects of sleep deprivation. Sleep deprivation rapidly upregulates
several plasticity-related genes, effects that are noradrenergically mediated; these
are the very same genes that are upregulated by chronic antidepressants. Thus, activating the norepinephrine system during REM sleep (by
infusing an α2 antagonist) may allow an interaction with a primed, sensitized postsynaptic milieu,
thereby rapidly increasing the expression of plasticity genes and consequently a rapid
antidepressant response.
Keywords
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Article info
Publication history
Accepted:
August 12,
2002
Received in revised form:
August 2,
2002
Received:
April 1,
2002
Identification
Copyright
© 2002 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
