Too little sleep gradually desensitizes the serotonin 1A receptor system.
OBJECTIVE
In our 24-hour society, frequently disrupted and restricted sleep is a rapidly increasing problem that may contribute to the development of diseases such as depression. One of the proposed neurobiological mechanisms underlying depression is a disturbance in the brain's serotonergic neurotransmission, particularly a desensitization of the serotonin (5-HT)1A receptor system. However, a relationship between chronic sleep loss and changes in (5-HT)1A receptors has not been established yet. Therefore, in the present study, we experimentally tested the hypothesis that chronic sleep restriction leads to desensitization of the (5-HT)1A receptor system.


METHODS
Rats were subjected to a schedule of restricted sleep allowing them 4 hours of sleep per day. Sleep restriction was achieved by placing the animals in slowly rotating wheels. The sensitivity of the (5-HT)1A receptor system was examined by measuring the hypothermic response to a standard injection of a 1A agonist.


RESULTS
After 2 days of restricted sleep, the sensitivity of the (5-HT)1A receptor system was not yet affected; however, after 8 days of sleep restriction, it was desensitized. Control experiments indicated that the effect of sleep restriction was not due to forced activity or stress. Importantly, the desensitization of the (5-HT)1A system persisted for many days even with unlimited recovery sleep. Normalization occurred gradually but required at least 7 days.


CONCLUSIONS
Chronic sleep restriction causes a gradual and persistent desensitization of the (5-HT)1A receptor system. This finding provides a link between chronic sleep loss and sensitivity for disorders that are associated with altered serotonergic neurotransmission.
Roman
Viktor
V
Department of Molecular Neurobiology, University, of Groningen, Haren, The Netherlands.
Walstra
Irene
I
Luiten
Paul G M
PG
Meerlo
Peter
P
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002908:Chronic Disease; D003863:Depression / Q000503:physiopathology; D018450:Disease Progression; D007279:Injections, Subcutaneous; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage; D012892:Sleep Deprivation / Q000175:diagnosis* / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects
D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin