Journal
SLEEP
Volume 26, Issue 8, Pages 943-947Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/sleep/26.8.943
Keywords
sleep; anandamide; adenosine; cannabinoids; insomnia; microdialysis
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Funding
- NIA NIH HHS [AG09975, AG15853] Funding Source: Medline
- NIMH NIH HHS [MH55772] Funding Source: Medline
- NINDS NIH HHS [NS30140] Funding Source: Medline
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Study Objectives: The principal component of marijuana, delta-9-tetrahydrocannabinol increases sleep in humans. Endogenous cannabinoids, such as N-arachidonoylethanolamine (anandamide), also increase sleep. However, the mechanism by which these molecules promote sleep is not known but might involve a sleep-inducing molecule such as adenosine. Microdialysis samples were collected from the basal forebrain in order to detect levels of adenosine before and after injection of anandamide. Design: Rats were implanted for sleep studies, and a cannula was placed in the basal forebrain to collect microdialysis samples. Samples were analyzed using high-performance liquid chromatography. Settings: Basic neuroscience research laboratory. Participants and Interventions: Three-month-old male F344 rats. At the start of the lights-on period, animals received systemic injections of dimethyl sulfoxide (vehicle), anandamide, SR141716A (cannabinoid receptor 1 [CB1] antagonist), or SR141716A and anandamide. One hour after injections, microdialysis samples were collected (5 muL) from the basal forebrain every hour over a 20-minute period for 5 hours. The samples were immediately analyzed via high-performance liquid chromatography for adenosine levels. Sleep was also recorded continuously over the same period. Measurements and Results: Anandamide increased adenosine levels compared to vehicle controls with the peak levels being reached during the third hour after drug injection. There was a significant increase in slow-wave sleep during the third hour. The induction in sleep and the rise in adenosine were blocked by the CB1-receptor antagonist, SR141716A. Conclusions: Anandamide increased adenosine levels in the basal fore-brain and also increased sleep. The soporific effects of anandamide were mediated by the CB1 receptor, since the effects were blocked by the CB1-receptor antagonist. These findings identify a potential therapeutic use of endocannabinoids to induce sleep in conditions where sleep may be severely attenuated.
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