Analgesic tolerance induced by repeated morphine injections induces cross-tolerance to the analgesic effect of orexin-A in rats. Issue 3 (7th February 2018)

• Record Type: Journal Article
• Authors: Azhdari-Zarmehri, Hassan; Ghasemi, Elmira; Heidari-Oranjaghi, Nima; Sadegh, Mehdi
• Is Part Of: NeuroReport. Volume 29:Issue 3(2018)
• Publication Date: 2018-02-07
• Subjects: antinociception -- hot plate -- hypocretin -- opioids -- pain; Neurosciences -- Periodicals; Nervous system -- Periodicals; Neurophysiology -- Periodicals; Nervous System Diseases -- Periodicals; Nervous System Physiological Phenomena -- Periodicals; Neurosciences -- Periodicals; 616.805
• DOI: 10.1097/WNR.0000000000000964
• Languages: English
• ISSNs: 0959-4965

Abstract

Abstract : Repeated administration of morphine or orexin-A produces tolerance to their antinociceptive effects. We investigated the possible incidence of cross-tolerance between orexin-A and morphine. Adult male Sprague-Dawley rats (200–250 g) were used. Under deep anesthesia, a stereotaxic apparatus was used to implant a 23 G cannula into the lateral ventricle for an intracerebroventricular (ICV) microinjection. The antinociceptive effect of three different doses of orexin-A (5, 20, and 40 µM; dissolved in 5 µl sterile saline; ICV) was examined using the hot-plate test at 15, 30, 60, and 90 min after infusion. To evaluate tolerance, orexin-A (20 µM; ICV) or morphine (10 mg/kg; intraperitoneal) was administered for 7 consecutive days (twice per day) and the analgesic response was assessed at days 1, 4, and 7. Cross-tolerance was investigated at day 8 with a single injection of morphine (10 mg/kg; intraperitoneal) to the repeated orexin-A group and a single microinjection of orexin-A (20 µM; ICV) to the repeated morphine group. Analgesic responses were then examined. Administration of both orexin-A and morphine produced significant antinociception at day 1 ( P <0.001 compared with the saline group). However, a significant reduction in the analgesic effects of both morphine and orexin-A appeared at day 7, following repeated administration ( P <0.01). Orexin-A microinjection at day 8 in the repeated morphine group did not result in significant antinociception ( P >0.05), whereas morphine injection in the repeated orexin-A group at day 8 showed a significant analgesic effect ( P <0.001). These results indicate cross-tolerance to the analgesic effect of orexin-A following morphine tolerance.