Nonpeptide Orexin-2 Receptor Agonist Attenuates Morphine-induced Sedative Effects in Rats
| Autor: | Yugo Tagaito, Naohito Shimoyama, Hiroshi Nagase, Satoshi Toyama, Tsuyoshi Saitoh, Masashi Yanagisawa, Megumi Shimoyama |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Agonist Reflex Startle medicine.medical_specialty Startle response medicine.drug_class Motor Activity Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Orexin Receptors Internal medicine medicine Animals Hypnotics and Sedatives Orexins Aniline Compounds Dose-Response Relationship Drug Morphine medicine.diagnostic_test business.industry Respiration Electroencephalography Orexin receptor Rats Orexin Dose–response relationship 030104 developmental biology Anesthesiology and Pain Medicine Endocrinology Sedative Benzamides Wakefulness business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Anesthesiology. 128:992-1003 |
| ISSN: | 0003-3022 |
| DOI: | 10.1097/aln.0000000000002161 |
| Popis: | Background Sleepiness and decrease in attention are dose-limiting side effects of opioids. The orexin/hypocretin system plays an important role in maintaining wakefulness. This study aimed to explore the potential of a nonpeptide orexin receptor agonist to alleviate morphine-induced sedative effects. Methods Morphine sedative effects were evaluated as changes in electroencephalogram (EEG), locomotor activity, and acoustic startle response in rats (n = 5 to 9 per group). Effects of intracerebroventricular orexin-A and systemic orexin type-2 receptor agonist, YNT-185, on EEG changes induced by morphine were examined. Furthermore, the authors examined effects of morphine administered with or without YNT-185 on locomotor activity and on acoustic startle response. Results Morphine-induced, frequent, short epochs of increased power (total epoch duration: 0.5 [0.0 to 8.0] s/10 min during baseline vs. 74.0 [49.0 to 115.0] s/10 min during the post–morphine administration period; P = 0.012). EEG analyses revealed that morphine-induced, high-amplitude, slow activity (increase in spectral power of frequencies less than 15 Hz, baseline vs. postmorphine; P < 0.001). Orexin-A and YNT-185 attenuated these changes. Locomotor activity decreased after morphine (268 [103 to 889] ambulatory movement counts during baseline period [20 min] vs. 138 [7 to 434] counts during 40 to 59 min postadministration; P = 0.012), but did not change after morphine with YNT-185 (363 [121 to 636] vs. 864 [381 to 1092] counts, difference within morphine + YNT-185 group; P = 0.071). Startle response latency was longer after morphine (26 [20 to 28] ms) than after morphine with YNT-185 (17 [16 to 18] ms; P = 0.012). Conclusions Orexin-A and/or YNT-185 attenuated morphine-induced sedative effects assessed by EEG changes and behavioral measures in rats. The authors’ results suggest that orexin-2 receptor activation alleviates morphine-induced sedative effects. |
| Databáze: | OpenAIRE |
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