title: Disharmony between wake- and respiration-promoting activities: effects of modafinil on ventilatory control in rodents.
abstract: Modafinil is a wake-promoting drug and has been widely used for daytime sleepiness in patients with narcolepsy and other sleep disorders. A recent case series reported that daily oral modafinil alleviated hypercapnic respiratory failure in patients with COPD. However, the precise action of modafinil on respiration such as hypercapnic and/or hypoxic ventilatory responses remains unclear. The aim of this study is to clarify the effect of modafinil on the ventilatory control.
  
  
  
  We investigated the hypothesis that modafinil enhances resting ventilation as well as the stimulatory ventilatory responses to hypercapnia and hypoxia. We addressed the issue by examining minute ventilation, respiratory rate and volume components using plethysmography, combined with a concurrent EEG monitoring of the level of wakefulness before and after administration of modafinil in two doses of 100 mg/kg and 200 mg/kg in unanesthetized mice. In addition, we monitored the effect of the lower dose of modafinil on mice locomotor activity in a freely moving condition by video-recording.
  
  
  
  Wakefulness, locomotor activity and variability of the breathing pattern in tidal volume were promoted by both doses of modafinil. Neither dose of modafinil increased the absolute values of resting ventilation or promoted the ventilatory responses to hypercapnia and hypoxia. Rather, higher dose of modafinil slightly suppressed respiratory rate in room air condition.
  
  
  
  Modafinil is conducive to the state of wakefulness but does not augment resting ventilation or the hyperventilatory responses to chemical stimuli in unanesthetized rodents.
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba city, Chiba, 260-8670, Japan. jirotera@chiba-u.jp.|Clinical Research Center, Murayama Medical Center, 2-37-1 Gakuen, Musashimurayama, Tokyo, 208-0011, Japan. jirotera@chiba-u.jp.
authors.forename: Jiro
authors.initials: J
authors.lastname: Terada
authors.affiliation: Clinical Research Center, Murayama Medical Center, 2-37-1 Gakuen, Musashimurayama, Tokyo, 208-0011, Japan.|Department of Biomedical Engineering, Graduate School of Science and Engineering, Toyo University, 2100 Kujirai, Kawagoe, Saitama, 350-8585, Japan.
authors.forename: Isato
authors.initials: I
authors.lastname: Fukushi
authors.affiliation: Clinical Research Center, Murayama Medical Center, 2-37-1 Gakuen, Musashimurayama, Tokyo, 208-0011, Japan.|Fujita Memorial Nanakuri Institute, Fujita Health University, 423 Oodori-cho, Tsu, Mie, 514-1296, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Clinical Research Center, Murayama Medical Center, 2-37-1 Gakuen, Musashimurayama, Tokyo, 208-0011, Japan.|Department of Pediatrics, School of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Hasebe
authors.affiliation: Clinical Research Center, Murayama Medical Center, 2-37-1 Gakuen, Musashimurayama, Tokyo, 208-0011, Japan.|Opole Medical School, 68 Katowicka Street, Opole, 45-060, Poland.
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Pokorski
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba city, Chiba, 260-8670, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tatsumi
authors.affiliation: Clinical Research Center, Murayama Medical Center, 2-37-1 Gakuen, Musashimurayama, Tokyo, 208-0011, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Okada
mesh_terms: D000204:Activity Cycles / Q000187:drug effects*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D004195:Disease Models, Animal; D006935:Hypercapnia / Q000188:drug therapy / Q000503:physiopathology; D000860:Hypoxia / Q000188:drug therapy / Q000503:physiopathology; D008124:Locomotion / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D000077408:Modafinil; D012123:Pulmonary Ventilation / Q000187:drug effects*; D012119:Respiration / Q000187:drug effects*; D013997:Time Factors; D014741:Video Recording; D064690:Wakefulness-Promoting Agents / Q000494:pharmacology*
chemical_list: D001559:Benzhydryl Compounds; D064690:Wakefulness-Promoting Agents; D000077408:Modafinil
keywords: Breathing; Electroencephalogram; Hypercapnic ventilatory response; Hypoxic ventilatory response; Narcolepsy; Respiratory failure; Vigilance; Wake-promoting drug