オレキシン受容体拮抗薬で睡眠誘導されたマウスは、睡眠中においても危機的状況下では覚醒能力を保持することができる

• Material Type: 博士論文
• Title: オレキシン受容体拮抗薬で睡眠誘導されたマウスは、睡眠中においても危機的状況下では覚醒能力を保持することができる
• Author/Editor: 岩川, 昌平
• Author Heading: 岩川, 昌平 イワカワ, ショウヘイ
• Publication, Distribution, etc.: Frontiers Media S.A.
• Alternative Title: Orexin Receptor Blockade-Induced Sleep Preserves the Ability to Wake in the Presence of Threat in Mice
• Degree grantor/type: 鹿児島大学
• Date Granted: 2020-03-12
• Dissertation Number: 甲総研第543号
• Degree Type: 博士(医学); Doctor of Philosophy in Medical Science
• Text Language Code: eng
• Subject Heading: orexin; hypocretin; hypnotics; dual orexin receptor antagonist; triazolam; aversive stimuli
• Target Audience: 一般
• Note (General): 博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨; Retention of the ability to wake from sleep in response to dangerous situations is an ideal characteristic of safe hypnotics. We studied the effects of a dual orexin receptor antagonist-22 (DORA-22) and the GABA-A receptor modulator, triazolam, on the ability to wake in response to aversive stimuli. We examined four modalities of sensory inputs, namely, auditory (ultrasonic sound), vestibular (trembling), olfactory (predator odor), and autonomic (hypoxia) stimuli. When the mice fell asleep, one of the four stimuli was applied for 30 s. In the case of auditory stimulation, latency to arousal following vehicle, DORA-22, and triazolam administration was 3.0 (2.0–3.8), 3.5 (2.0–6.5), and 161 (117–267) s (median and 25–75 percentile in the parentheses, n = 8), respectively. Latency to return to sleep after arousal was 148 (95–183), 70 (43–98), and 60 (52–69) s, respectively. Similar results were obtained for vestibular and olfactory stimulation. During the hypoxic stimulation, latencies for arousal and returning to sleep were not significantly different among the groups. The findings of this study are consistent with the distinct mechanisms of these sleep promoting therapies; GABA-A receptor activation by triazolam is thought to induce widespread central nervous system (CNS) suppression while DORA-22 more specifically targets sleep/wake pathways through orexin receptor antagonism. These data support the notion that DORA-22 preserves the ability to wake in response to aversive and consciousness-inducing sensory stimuli, regardless of modality, while remaining effective in the absence of threat. This study provides a unique and important safety evaluation of the potential for certain hypnotics. Shouhei Iwakawa, Yuichi Kanmura and Tomoyuki Kuwaki Orexin Receptor Blockade-Induced Sleep Preserves the Ability to Wake in the Presence of Threat in Mice Frontiers in Behavioral Neuroscience, 2019 https://doi.org/10.3389/fnbeh.2018.00327
• Format (IMT): application/pdf
• Source: Diss_岩川_昌平_ISK543_2019 （fulltext）; https://ir.kagoshima-u.ac.jp/record/15173/files/Diss_%E5%B2%A9%E5%B7%9D_%E6%98%8C%E5%B9%B3_ISK543_2019.pdf
• Access Restrictions: インターネット公開
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 鹿児島大学 : 鹿児島大学リポジトリ