Too little sleep gradually desensitizes the serotonin 1A receptor system

Roman, V., Walstra, I., Luiten, PGM. & Meerlo, P., 2005, In : Sleep. 28, 12, p. 1505-1510

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  • Viktor Roman
  • Irene Walstra
  • PGM Luiten
  • P Meerlo

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.

Original languageEnglish
Pages (from-to)1505-1510
Issue number12
Publication statusPublished - 2005


  • short sleep, sleep loss, sleep deprivation, sleep restriction, sleep fragmentation, sleep disruption, sleep disturbance, sleep disorder, insomnia, depression, mood disorder, affective disorder, psychopathology, psychiatric disorder, disease, serotonergic system, serotonin, serotonin receptor, serotonin 1A receptor, 5-HT1A receptor, 8-OH-DPAT, forced activity, stress, stress hormones, glucocorticoids, corticosterone, radiotelemetry, body temperature, hypothermia, hypothermic response

ID: 1158311