Journal article
Insomnia Caused by Serotonin Depletion is Due to Hypothermia
Sleep (New York, N.Y.), Vol.38(12), pp.1985-1993
12/01/2015
DOI: 10.5665/sleep.5256
PMCID: PMC4667392
PMID: 26194567
Abstract
Serotonin (5-hydroxytryptamine, 5-HT) neurons are now thought to promote wakefulness. Early experiments using the tryptophan hydroxylase inhibitor para-chlorophenylalanine (PCPA) had led to the opposite conclusion, that 5-HT causes sleep, but those studies were subsequently contradicted by electrophysiological and behavioral data. Here we tested the hypothesis that the difference in conclusions was due to failure of early PCPA experiments to control for the recently recognized role of 5-HT in thermoregulation.
Adult male C57BL/6N mice were treated with PCPA (800 mg/kg intraperitoneally for 5 d; n = 15) or saline (n = 15), and housed at 20 °C (normal room temperature) or at 33 °C (thermoneutral for mice) for 24 h. In a separate set of experiments, mice were exposed to 4 °C for 4 h to characterize their ability to thermoregulate.
PCPA treatment reduced brain 5-HT to less than 12% of that of controls. PCPA-treated mice housed at 20 °C spent significantly more time awake than controls. However, core body temperature decreased from 36.5 °C to 35.1 °C. When housed at 33 °C, body temperature remained normal, and total sleep duration, sleep architecture, and time in each vigilance state were the same as controls. When challenged with 4 °C, PCPA-treated mice experienced a precipitous drop in body temperature, whereas control mice maintained a normal body temperature.
These results indicate that early experiments using para-chlorophenylalanine that led to the conclusion that 5-hydroxytryptamine (5-HT) causes sleep were likely confounded by hypothermia. Temperature controls should be considered in experiments using 5-HT depletion.
Details
- Title: Subtitle
- Insomnia Caused by Serotonin Depletion is Due to Hypothermia
- Creators
- Nicholas M Murray - Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, IAGordon F Buchanan - Veterans Affairs Medical Center, West Haven, CTGeorge B Richerson - Veterans Affairs Medical Center, Iowa City, IA
- Resource Type
- Journal article
- Publication Details
- Sleep (New York, N.Y.), Vol.38(12), pp.1985-1993
- Publisher
- United States
- DOI
- 10.5665/sleep.5256
- PMID
- 26194567
- PMCID
- PMC4667392
- ISSN
- 0161-8105
- eISSN
- 1550-9109
- Grant note
- K08 NS069667 / NINDS NIH HHS K08NS069667 / NINDS NIH HHS R01 HD052772 / NICHD NIH HHS P20NS076916 / NINDS NIH HHS P01HD36379 / NICHD NIH HHS U01 NS090414 / NINDS NIH HHS R01HD052772 / NICHD NIH HHS
- Language
- English
- Date published
- 12/01/2015
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984013110502771
Metrics
23 Record Views