Disharmony between wake- and respiration-promoting activities: Effects of modafinil on ventilatory control in rodents

Jiro Terada, Isato Fukushi, Kotaro Takeda, Yohei Hasebe, Mieczyslaw Pokorski, Koichiro Tatsumi, Yasumasa Okada

Research output: Contribution to journalArticle

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: Modafinil is conducive to the state of wakefulness but does not augment resting ventilation or the hyperventilatory responses to chemical stimuli in unanesthetized rodents.

Original languageEnglish
Article number148
JournalRespiratory Research
Volume17
Issue number1
DOIs
Publication statusPublished - 14-11-2016

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Rodent Control
Respiration
Ventilation
Wakefulness
Hypercapnia
Locomotion
Respiratory Rate
Wakefulness-Promoting Agents
modafinil
Narcolepsy
Video Recording
Plethysmography
Tidal Volume
Respiratory Insufficiency
Chronic Obstructive Pulmonary Disease

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine

Cite this

Terada, Jiro ; Fukushi, Isato ; Takeda, Kotaro ; Hasebe, Yohei ; Pokorski, Mieczyslaw ; Tatsumi, Koichiro ; Okada, Yasumasa. / Disharmony between wake- and respiration-promoting activities : Effects of modafinil on ventilatory control in rodents. In: Respiratory Research. 2016 ; Vol. 17, No. 1.
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Disharmony between wake- and respiration-promoting activities : Effects of modafinil on ventilatory control in rodents. / Terada, Jiro; Fukushi, Isato; Takeda, Kotaro; Hasebe, Yohei; Pokorski, Mieczyslaw; Tatsumi, Koichiro; Okada, Yasumasa.

In: Respiratory Research, Vol. 17, No. 1, 148, 14.11.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Disharmony between wake- and respiration-promoting activities

T2 - Effects of modafinil on ventilatory control in rodents

AU - Terada, Jiro

AU - Fukushi, Isato

AU - Takeda, Kotaro

AU - Hasebe, Yohei

AU - Pokorski, Mieczyslaw

AU - Tatsumi, Koichiro

AU - Okada, Yasumasa

PY - 2016/11/14

Y1 - 2016/11/14

N2 - Background: 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. Methods: 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. Results: 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. Conclusions: Modafinil is conducive to the state of wakefulness but does not augment resting ventilation or the hyperventilatory responses to chemical stimuli in unanesthetized rodents.

AB - Background: 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. Methods: 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. Results: 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. Conclusions: Modafinil is conducive to the state of wakefulness but does not augment resting ventilation or the hyperventilatory responses to chemical stimuli in unanesthetized rodents.

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