title: Multiple sleep alterations in mice lacking cannabinoid type 1 receptors.
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.
authors.affiliation: PRISM lab, Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Silvani
authors.affiliation: PRISM lab, Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Berteotti
authors.affiliation: PRISM lab, Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bastianini
authors.affiliation: PRISM lab, Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Lo Martire
authors.affiliation: 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.
authors.forename: Roberta
authors.initials: R
authors.lastname: Mazza
authors.affiliation: 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.
authors.forename: Uberto
authors.initials: U
authors.lastname: Pagotto
authors.affiliation: 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.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Quarta
authors.affiliation: PRISM lab, Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zoccoli
mesh_terms: D000818:Animals; D001143:Arousal / Q000502:physiology; D001835:Body Weight; D059305:Diet, High-Fat / Q000009:adverse effects; D004569:Electroencephalography; D004576:Electromyography; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology*; D012892:Sleep Deprivation / Q000503:physiopathology*; D012894:Sleep Stages / Q000502:physiology*; D012895:Sleep, REM; D014851:Wakefulness / Q000502:physiology
chemical_list: D043884:Receptor, Cannabinoid, CB1