(2018) Analgesic tolerance induced by repeated morphine injections induces cross-tolerance to the analgesic effect of orexin-A in rats. Neuroreport. pp. 224-228. ISSN 1473-558X (Electronic) 0959-4965 (Linking)
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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 microM; dissolved in 5 microl 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 microM; 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 microM; 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.
Item Type: | Article |
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Keywords: | - |
Page Range: | pp. 224-228 |
Journal or Publication Title: | Neuroreport |
Journal Index: | ISI, Pubmed, Scopus |
Volume: | 29 |
Number: | 3 |
Identification Number: | 10.1097/WNR.0000000000000964 |
ISSN: | 1473-558X (Electronic) 0959-4965 (Linking) |
Depositing User: | دکتر محبوبه عبداللهی |
URI: | http://eprints.thums.ac.ir/id/eprint/331 |
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