Analgesic tolerance induced by repeated morphine injections induces cross-tolerance to the analgesic effect of orexin-A in rats

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 …