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Information Seminar Paper

Title

THE EFFECTS OF MIFEPRISTONE AND METYRAPONE ON MORPHINE WITHDRAWAL- INDUCED MEMORY DEFICIT IN MICE

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Abstract

 Introduction: Morphine withdrawal leads to an increase in corticosterone concentration in plasma. Studies in human opiate addicts indicate that many brain areas are hypo functional during withdrawal that may relate to the cognitive deficits found in them. In this study, the effects of metyrapone and mifepristone were studied on memory deficit following morphine withdrawal.Methods: Mice were made dependent by increasing doses of morphine (30-90 mg/kg, s.c.) twice daily for three days. Withdrawal was elicited by injection of naloxone (0.1 mg/kg, i.p.) three hours after last morphine injection. Mifepristone (50,100mg/kg) and metyrapone (12.5, 25mg/kg) were used before recognition testing and effects were compared with the control groups. Memory performance was tested by using object recognition task.Results: Mean of recognition Index (RI) for mice receiving 50,100mg/kg mifepristone or vehicle, were -8.6, 30 and -34 respectively. Mifepristone 100mg/kg could significantly (P<0.05) improve RI , Mean of RI for mice receiving 12.5, 25mg/kg metyrapone or vehicle, were 42.7, -1.33 and -4.33 respectively which shows a significant improve of RI (P<0.05) for metyrapone 12.5mg/kg.Conclusion: These results show that increased glucocorticoid concentration can be involved in memory deficit caused by morphine withdrawal. So metyrapone by inhibiting glucocorticoid formation and mifepristione by inhibiting glucocorticoid receptors can be useful for preventing memory deficit following morphine withdrawal.

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