Ascorbic acid inhibits the acquisition and expression of morphine-induced conditioned place preference and sensitization in male Swiss-Webster mice

Introduction: Ascorbic acid is shown to reduce the signs of opioid dependence and addiction. The present experiments investigated the possible influence of ascorbic acid in acquiring and expressing morphine conditioned place preference (CPP) and sensitization in mice.Methods: Male Swiss-Webster mice (20-25 g) were used. The unbiased method and an open field procedure were conducted for place preference and sensitization studies, respectively. Animals received different doses of morphine (1, 5, 10, and 20 mg/kg), ascorbic acid (1, 10, 100, and 1000 mg/kg), or saline (10 ml/kg) for place preference studies. Ascorbic acid was injected into the animals 20 min before each morphine (5 mg/kg) injection (acquisition) or 20 min before the test of morphine CPP (expression). Mice received morphine (5 mg/ kg) for three consecutive days, followed by five resting days for sensitization. Animals' hyperactivity after morphine (1 mg/kg) challenge dose confirmed the sensitization. Ascorbic acid was administered 20 min before each morphine (5 mg/kg) injection (acquisition) or 20 min before each morphine challenge dose (1 mg/kg) administration on the test day (expression).Results: Morphine induced significant place preference dose-dependently. Furthermore, intraperitoneal (i.p.) administration of ascorbic acid failed to induce any aversion or preference effects. Ascorbic acid reduced the expression and acquisition of morphine place conditioning. Intraperitoneal injections of ascorbic acid also reduced the expression and acquisition of morphine sensitization. Conclusion: Ascorbic acid could affect the motivational effects of morphine in mice. The exact mechanism by which the vitamin reduces the morphine effect must be evaluated in future studies.