Evaluation of Vitamine C and Citicoline on morphine-induced tolerance in male mice

Abstract

Introduction: Long-term exposure to opiates induces tolerance to their analgesic effects. There are some discovered mechanisms of vitamin C and citicoline indicating possible inhibitory effects on "glutaminergic system", of which hyperactivation will result in tolerance. Our study evaluated the probable potential effects of these two drugs on morphine-induced tolerance. Aim: The principle goal was to evaluate outcomes of i.p. injection of vitamin C and citicoline on morphine tolerance in male mice. Methods: Nine groups of male mice (n=8 in each group, weight= 20-30 g) were administrated the following daily regimens for 4 days: 1) Saline (10 ml/kg, ip) + Saline (10 ml/kg, ip)

2) Saline (10 ml/kg , ip) + Morphine (50 mg/kg, ip)

3,4,5) Citicoline (5,10,15 mg/kg, ip) + Morphine (50 mg/kg, ip)

6,7,8) Vitamine C (25, 50,75 mg/kg, ip) + Morphine (50 mg/kg, ip)

9) Citicoline (10 mg/kg, ip) + Vitamine C (50 mg/kg, ip) + Morphine (50 mg/kg, ip) In each group antinociceptive response of a test dose of morphine (9 mg/kg, ip) was assayed 24 hours after the last dose of morphine (50 mg/kg, ip) by the Hot-plate test, conducted within one hour, at minutes (0, 15, 30, 45, 60). Then blood sampling was performed. Plasma serums were provided and stored in -70 ̊c until MDA and TAC assays with relevant kits. Results: Although statistical analysis showed a significant reduction of morphine tolerance in mice by groups 7 and 8 of vitamin C with disirable p values than control group (daily administered morphine 50 mg/kg, ip), no significant difference was occurred by groups of citicoline, combined treatment, neither by MDA and TAC concentrations. Conclusion: The utilization of vitamin C could be considerably beneficial to attenuate morphine-induced tolerance.