Multiple sleep alterations in mice lacking cannabinoid type 1 receptors

PLoS One. 2014 Feb 20;9(2):e89432. doi: 10.1371/journal.pone.0089432. eCollection 2014.

Abstract

Cannabinoid type 1 (CB1) receptors are highly expressed in the brain and play a role in behavior control. Endogenous cannabinoid signaling is modulated by high-fat diet (HFD). We investigated the consequences of congenital lack of CB1 receptors on sleep in mice fed standard diet (SD) and HFD. CB1 cannabinoid receptor knock-out (KO) and wild-type (WT) mice were fed SD or HFD for 4 months (n = 9-10 per group). Mice were instrumented with electroencephalographic (EEG) and electromyographic electrodes. Recordings were performed during baseline (48 hours), sleep deprivation (gentle handling, 6 hours), sleep recovery (18 hours), and after cage switch (insomnia model paradigm, 6 hours). We found multiple significant effects of genotype on sleep. In particular, KO spent more time awake and less time in non-rapid-eye-movement sleep (NREMS) and rapid-eye-movement sleep (REMS) than WT during the dark (active) period but not during the light (rest) period, enhancing the day-night variation of wake-sleep amounts. KO had slower EEG theta rhythm during REMS. REMS homeostasis after sleep deprivation was less effective in KO than in WT. Finally, KO habituated more rapidly to the arousing effect of the cage-switch test than WT. We did not find any significant effects of diet or of diet x genotype interaction on sleep. The occurrence of multiple sleep alterations in KO indicates important roles of CB1 cannabinoid receptors in limiting arousal during the active period of the day, in sleep regulation, and in sleep EEG in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arousal / physiology
  • Body Weight
  • Diet, High-Fat / adverse effects
  • Electroencephalography
  • Electromyography
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptor, Cannabinoid, CB1 / physiology*
  • Sleep Deprivation / physiopathology*
  • Sleep Stages / physiology*
  • Sleep, REM*
  • Wakefulness / physiology

Substances

  • Receptor, Cannabinoid, CB1

Grants and funding

This work was funded by Bologna University (RFO 2010 and 2011 http://www.unibo.it/Portale/Ricerca/Servizi+Docenti+Ricercatori/finanziamentinaz/RFO+-+Finanziamento+alla+ricerca+di+base.htm). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.