UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

The effects of sleep deprivation on 5-HT1A and 5-HT2A receptor expression in the hippocampus Suen, Yat Him Vincent


Sleep deprivation (SD) is becoming increasingly prevalent in our busy society. Teenagers, shift workers, and hard working professionals, among others, are all victims of this epidemic. The consequences of SD are dire. In the short term, they include cognitive deficits, impaired memory consolidation, experiencing negative mood states, and loss of homeostatic control. In a chronic context, SD is often associated with severe psychiatric disorders such as depression, psychosis and anxiety. Recent studies have found that the expression and heterodimerization of metabotropic glutamate receptors 1α (mGluR1α) and γ-aminobutyric acid B receptors (GABABR) were altered in the rat hippocampus following 12 hours of SD. Whether SD induces similar changes in other G protein-coupled receptors is unknown. 5-hydroxytryptamine (5-HT) regulates sleep, emotion, mood, and memory. Its receptors, particularly 5-HT₁A and 5-HT₂A, have been linked to multiple psychiatric disorders, as commonly used antidepressants, antipsychotics and anxiolytics theoretically exert their actions through these receptors. In this study, western blot and peroxidise immunohistochemistry revealed that 5-HT₁A expression was increased in rat hippocampus following 12 hours of SD, specifically in the CA1 pyramidal layer. This up-regulation persisted despite 24 hours of recovery sleep, and recovered partially after 48 hours. 5-HT₂A expression in whole hippocampal lysate was detected to be unchanged by western blot following 12 hours of SD, but immunohistochemistry revealed increased expression in the CA1 pyramidal layer, suggesting that 5-HT₂A may be down-regulated in other regions of the hippocampus. Increased 5-HT₂A expression in the CA1 pyramidal layer recovered back to control levels within 24 hours of recovery. The action of the agonist 5-HT on the field excitatory post-synaptic potentials (fEPSPs) of CA1 neurons was also investigated in hippocampal slices. 5-HT dose-dependently suppressed fEPSPs – an effect which was enhanced by 12 hours of SD, but the enhancement was reverted within 24 hours of sleep recovery. Heterodimerization between either 5-HT₁A or 5-HT₂A and either of mGluR1α, GABABR1 or GABABR2 was investigated by co-immunoprecipitation, but no evidence of heterodimers was found. These results suggest increased 5-HT transmission in the hippocampus following SD, which could potentially lead to the development of psychiatric disorders and has consequences for drug dosing.

Item Citations and Data


Attribution-NonCommercial-NoDerivs 2.5 Canada