An Evaluation of the Role of OTC [(−)-2-Oxo-4-thiazolidinecarboxylic acid] in Acquisition and Expression of Morphine Dependence in Male NMRI Mice

Abstract

BACKGROUND AND OBJECTIVE: In morphine dependence, the concentration of natural antioxidants decreases and glutathione is one of the most important ones. Therefore, antioxidants may reduce morphine withdrawal symptoms. Therefore, the present study was conducted to analyze the effect of various concentrations of OTC [(−)-2-Oxo-4-thiazolidinecarboxylic acid] (glutathione transferase activator) on acquisition and expression of morphine dependence. METHODS: In this experimental study, small male NMRI mice (20 – 30 g) were divided into 9 groups (n = 8). The mice became morphine-dependent using Marshall Method. The animals were administered with various concentrations of OTC (5, 10, 20 mg/kg) on days of inducing dependence (reception) or days of test (expression). Two main symptoms of withdrawal syndrome (the number of jumps and the weight of stools) were evaluated by administration of naloxone. FINDINGS: Administration of naloxone in the mice that received morphine on previous days increased the weight of stools (0.62±0.2 and 0.3±0.05 in morphine and saline group, respectively) and the number of jumps (46±15 and 1±0.2 in morphine and saline group, respectively; p<0.01). OTC administration did not cause significant changes in the weight of stools and the number of jumps compared with saline group. OTC administration on days of reception increased the weight of stools and the number of jumps (0.53±0.01, 1.2±0.5, 1±0.04 and 0.62±0.01 in 5, 10, 20 mg/kg OTC and saline, respectively; p<0.01) and increased the number of jumps on days of test (p<0.01). CONCLUSION: Results of the study demonstrated that stimulating glutathione transferase by OTC improves the acquisition of physical dependence to morphine.

Keywords

• Morphine
• Glutathione transferase
• Dependence
• Expression
• Marshall Method
• Diarrhea