TY - JOUR ID - 6270 TI - Repeated injections of orexin-A developed behavioral tolerance to its analgesic effects in rats JO - Iranian Journal of Basic Medical Sciences JA - IJBMS LA - en SN - 2008-3866 AU - Ghasemi, Elmira AU - Heidari-Oranjaghi, Nima AU - Azhdari-Zarmehri, Hassan AU - Sadegh, Mehdi AD - Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran AD - Department of Physiology, Zanjan University of Medical Sciences, Zanjan, Iran AD - Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran AD - Department of Physiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran Y1 - 2015 PY - 2015 VL - 18 IS - 12 SP - 1183 EP - 1188 KW - Anti-nociception KW - Hot plate KW - Orexin-A KW - Tolerance DO - 10.22038/ijbms.2015.6270 N2 - 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. UR - https://ijbms.mums.ac.ir/article_6270.html L1 - https://ijbms.mums.ac.ir/article_6270_fc2693fd0e1ef47a01d28656cca1763b.pdf ER -