Evaluation the effects of systemic administration of minocycline and riluzole on tolerance to morphine analgesic effect in rat

Abstract

Objectives: Chronic opiate administration induces tolerance to the analgesic effect. Several studies indicate that nitric oxide/ N-methyl D-aspartate pathway has important role on morphine induced tolerance. The main goal of this study was to evaluate the effects of systemic administration of Minocycline and Riluzole on Morphine induced tolerance in rat. Methods: Animals were divided in 8 groups (n=8) and received daily: Saline (1 ml/kg, ip) or {Saline (1ml/kg, ip) + Morphine (10 mg /kg, ip)} or {Minocycline (10, 20, 40 mg/kg, ip) + Morphine (10 mg/kg, ip)} or Minocycline (10 mg/kg, ip) or Tween 80 (2%) (1 ml/kg, ip) or {Tween 80 (2%) (1ml/kg- ip) + Morphine (10 mg /kg, ip)} or {Riluzole (4, 8, 12 mg/kg, ip) + Morphine (10 mg/kg, ip)} or Riluzole (12 mg/kg, ip). Nociception was assessed using hot-plate apparatus. The hot-plate latency was recorded when rat licked its hind paw. A baseline latency was determined daily, then drug was injected. After 30 minutes morphine was administrated and post-drug latency evaluated 30 minutes after the injection of Morphine. Results: Results showed that Minocycline (20, 40 mg/kg) and Minocycline (10 mg/kg), delayed the tolerance appearing time about 3 and 4 days respectively. Riluzole (8, 12 mg/kg) could postpone day of morphine tolerance for 5 days in comparison with control group. Conclusion: Interaction with nitric oxide system and glutamatergic pathway are the possible mechanisms of Minocycline and ability of Riluzole as a glutamate release inhibitor could be the major mechanism in attenuating the development of Morphine induced tolerance.