Timing is everything: does the robust upregulation of noradrenergically regulated plasticity genes underlie the rapid antidepressant effects of sleep deprivation?
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 alpha(2) 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.
Payne
Jennifer L
JL
Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Bethesda, Maryland 20892-1283, USA.
Quiroz
Jorge A
JA
Zarate
Carlos A
CA
Manji
Husseini K
HK
D000928:Antidepressive Agents / Q000008:administration & dosage; D015195:Drug Design; D005786:Gene Expression Regulation; D006801:Humans; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism; D009473:Neuronal Plasticity / Q000235:genetics*; D009638:Norepinephrine / Q000378:metabolism*; D012892:Sleep Deprivation / Q000503:physiopathology*; D012895:Sleep, REM / Q000502:physiology*; D015854:Up-Regulation
D000928:Antidepressive Agents; D009638:Norepinephrine