Multiple sleep alterations in mice lacking cannabinoid type 1 receptors.
PLoS ONE. 2014-02-20; 9(2): e89432
DOI: 10.1371/journal.pone.0089432
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Silvani A(1), Berteotti C(1), Bastianini S(1), Lo Martire V(1), Mazza R(2),
Pagotto U(2), Quarta C(2), Zoccoli G(1).
Author information:
(1)PRISM lab, Department of Biomedical and Neuromotor Sciences, Alma Mater
Studiorum – University of Bologna, Bologna, Italy.
(2)Endocrinology Unit and Center for Applied Biomedical Research, Department of
Medical and Surgical Sciences, S. Orsola University Hospital, Alma Mater
Studiorum – University of Bologna, Bologna, Italy.
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.
DOI: 10.1371/journal.pone.0089432
PMCID: PMC3930731
PMID: 24586776 [Indexed for MEDLINE]