title: Interleukin 1 receptor contributes to methamphetamine- and sleep deprivation-induced hypersomnolence.
abstract: Methamphetamine-induced wakefulness is dependent on monoamine transporter blockade. Subsequent to methamphetamine-induced wakefulness, the amount of time spent asleep and the depth of sleep are increased relative to baseline sleep. The mechanisms that drive methamphetamine-induced hypersomnolence are not fully understood. We recently observed that methamphetamine exposure elevates the expression of the sleep-promoting cytokine, interleukin-1β in CD11b-positive monocytes within the brain. Here, we sought to determine whether activation of the interleukin 1 receptor (IL1R) drives the increase in the depth and amount of sleep that occurs subsequent to methamphetamine-induced wakefulness. IL1R-deficient mice and wild type control mice were subjected to systemic methamphetamine (1 and 2mg/kg) and saline treatments. The wake-promoting effect of methamphetamine was modestly potentiated by IL1R-deficiency. Additionally, the increase in time spent in NREMS subsequent to methamphetamine-induced wakefulness in wild type mice was abolished in IL1R-deficient mice. The increase in time spent asleep after 3h of behaviorally enforced wakefulness was also abolished in IL1R-deficient mice. Increases in EEG slow wave activity triggered by methamphetamine and sleep deprivation were of equal magnitude in IL1R-deficient and wild type mice. These data demonstrate that IL1R activation contributes to hypersomnolence that occurs after sleep loss, whether that sleep loss is triggered pharmacologically by methamphetamine or through behavioral sleep deprivation.
authors.affiliation: WWAMI Medical Education Program and Department of Veterinary Comparative Anatomy, Pharmacology and Physiology, Washington State University, Spokane, WA 99202, United States.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Schmidt
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Wisor
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006970:Disorders of Excessive Somnolence / Q000209:etiology / Q000378:metabolism*; D004569:Electroencephalography; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D012892:Sleep Deprivation / Q000150:complications / Q000378:metabolism*; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
chemical_list: D017472:Receptors, Interleukin-1; D008694:Methamphetamine