Repeated injections of orexin-A developed behavioral tolerance to its analgesic effects in rats

Ghasemi, Elmira and Heidari-Oranjaghi, Nima and Azhdari-Zarmehri, Hassan and Sadegh, Mehdi (2015) Repeated injections of orexin-A developed behavioral tolerance to its analgesic effects in rats. Iranian Journal of Basic Medical Sciences, 18 (12). pp. 1183-1188.

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Objective(s):Reduction of pharmacological effectiveness or tolerance appears following repeated administration of many analgesic drugs. We investigated tolerance to anti-nociceptive effects of orexin-A, an endogenous potent analgesic peptide using the hot-plate test.Materials and Methods:Orexin-A was microinjected ICV (intracerebroventricular) with an interval of 12 hr for 7 continuous days and its anti-nociceptive responses were measured on days 1, 4 and 7 using the hot-plate test following the first day of administration. Orexin-A was used at a dose of 100 pmol to induce analgesic effects. Results:ICV administration of orexin-A produced an effective anti-nociception on the first day of experiment as measured by hot-plate 5, 15, and 30 min after the injection, in comparison with both baselines (hot-plate test one day before the beginning of orexin-A administration and control, saline-administrated group). However, repeated administration of orexin-A on the following days revealed a significant reduction in this analgesic effect during day 4 to day 7. However, to rule out any associative tolerance resulting from learning related to experimental procedures and/or environmental cues, a single injection of orexin-A was administrated to animals of control group (which were receiving saline during 7 days of experiments) and the analgesic effect was observed. Conclusion:These results, for the first time, indicated the appearance of tolerance to anti-nociceptive effects of orexin-A, following repeated administrations of this agent.

Item Type: Article
Subjects: QT physiology
Divisions: Journals > Iranian J Basic Medical Sciences
Depositing User: ijbms ijbms
Date Deposited: 02 Oct 2017 13:30
Last Modified: 02 Oct 2017 13:30

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