Ascorbic acid antagonizes nicotine-induced place preference and behavioral sensitization in female mice

Introduction: The influence of ascorbic acid on the nicotine-induced conditioned place preference (CPP) and behavioral sensitization was investigated in the present study. Methods: In a pilot study, place conditioning and locomotor activity were investigated after nicotine (0.25, 0.5, 0.75, 1, 1.5 and 2 mg/kg) or ascorbic acid (1, 10, 100 and 1000 mg/kg) administration. Different doses of ascorbic acid in conditioning days or on the test days were used. Behavioral sensitization was induced in animals by daily intraperitoneal administration of nicotine (0.25 mg/kg) for seven cosecutive days followed by one day interval. On 9th day, locomotor activity was induced by ineffective dose of nicotine (0.1 mg/kg). Ascorbic acid was injected 20 min before each injection of nicotine (acquisition of sensitization) or acutely 20 min before a challenge nicotine injection (expression of sensitization). Results: The results showed that intraperitoneal nicotine (1 mg/kg) administration can induce place preference whereas acute administration of the drug induces catalepsy. Administration of ascorbic acid did not induce place preference nor place aversion and also did not change the locomotor activity. Locomotor sensitization in mice was produced by intraperitoneal injection of nicotine (0.25 mg/kg) for 7 consecutive days. On the 9th day of experiments, activity of the mice was recorded after challenge with nicotine (0.1 mg/kg, i.p.). The senisitization was better achived when the ineffective dose of nicotine (0.1 mg/kg) was applied. Administration with ascorbic acid reduced both the acquisition and expression of nicotine-induced CPP. It was shown that ascorbic acid attenuated the acquisition of nicotine sensitization in a dose-independent manner but the expression of nicotineinduced sensitization was not affected by ascorbic acid. Conclusion: We conclude that ascorbic acid may interfere with nicotine-induced place preference and behavioral sensitization.