Study Objectives: 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-HT1A 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-HT1A receptor system.

Design: 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-HT1A 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-HT1A 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.