(2015) Repeated injections of orexin-A developed behavioral tolerance to its analgesic effects in rats. Iranian Journal of Basic Medical Sciences. pp. 1183-1188. ISSN 20083866
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Abstract
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, salineadministrated 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. © 2015, Mashhad University of Medical Sciences. All rights reserved.
Item Type: | Article |
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Keywords: | Anti‐nociception ; Hot plate ; Orexin‐A ; Tolerance |
Page Range: | pp. 1183-1188 |
Journal or Publication Title: | Iranian Journal of Basic Medical Sciences |
Journal Index: | ISI, Pubmed, Scopus |
Volume: | 18 |
Number: | 12 |
Publisher: | Mashhad University of Medical Sciences |
ISSN: | 20083866 |
Depositing User: | دکتر محبوبه عبداللهی |
URI: | http://eprints.thums.ac.ir/id/eprint/201 |
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