Salvia officinalis L. attenuates morphine analgesic tolerance and dependence in rats: possible analgesic and sedative mechanisms

Abstract

Background: Salvia officinalis L. (SO) has effects on the central nervous system, including anti-addiction properties that may involve an opioid mechanism. Objective: Effects of a hydroalcoholic extract of SO on nociception and on morphine-induced tolerance and dependence were evaluated in rats. Methods: Tolerance and dependence were induced by injection of morphine (10 mg/kg, s.c.) or escalating doses of morphine (2.5, 2.5, 5, 10, 20, 40 and 50 mg/kg, s.c.) twice daily for 7 days. SO (400, 600 and 800 mg/kg, i.g.) was administered before morphine. The tail-flick and naloxone precipitation withdrawal tests were used to evaluate tolerance and dependence. Sedative effects as well as total polyphenolic and flavonoid were also measured. Results: The morphine-treated group showed significant decrements in the percentage maximum possible effect (%MPE) on days 5 and 7 compared to the first day, illustrating morphine tolerance. Higher doses decreased morphine tolerance. Furthermore, SO (600 and 800 mg/kg) attenuated almost all of the withdrawal signs including weight loss, jumping, penis licking, teeth chattering, wet dog shakes, rearing, standing, sniffing, face grooming and paw tremor and increased sleep duration (64.5 ± 9.7, 100.3 ± 4.7, respectively). Total polyphenolic and flavonoid content of SO was 138 and 69 mg per g of dried extract, respectively. Conclusion: SO has antinociceptive effects and may decrease tolerance and dependence induced by repeated morphine administration. However, to determine whether treatment with SO blocks tolerance by interfering with neurobiological mechanisms that mediate the development of morphine tolerance will require further studies.