Evaluation of the effects of Sertralin and Spironolacton in morphine induced tolerance in male mice

Abstract

Introduction: Chronic use of opioid analgesics leads to tolerance to their analgesic effect. One of the reasons for tolerance is the increase in inflammatory factors and the increase in P-gp gene expression. Sertraline, as an SSRI drug, inhibits P-GP and on the other hand reduces cytokines effective in the phenomenon of tolerance. Spironolactone is also known as a potassium-sparing diuretic that has variable effects on P-gp.Objective: The objective of this study was to investigate the effects of chronic intraperitoneal injection of different doses of sertraline and spironolactone on the occurrence of tolerance to the analgesic effect of morphine in male mice.Methods: 81 male mice were randomly selected in 9 groups of 9 in the weight range of 20-30 grams and received the following drug regimens once a day for fourteen days.Different doses of sertraline with amounts (2.5-5-10 mg/kg ip), different doses of spironolactone with amounts (10-20-40 mg/kg ip), or a combination of two sertraline drugs with a dose of (2.5 mg/kg, ip) + spironolactone with a dose of (10 mg/kg,ip). Every day half an hour before the daily injection of morphine (25mg/kg ip) was injected into the mice. Then, on the 15th day, the anti-inflammatory effects caused by the morphine dose test (9mg/kg.ip) were evaluated in different groups by the Hot plate method.Results: The results indicated no significant effect on reducing tolerance in different doses of sertraline and spironolactone. In other words, none of the consumed amounts of sertraline and spironolactone exerted a significant effect in inhibiting the tolerance caused by morphine.Conclusion: Injections of 2.5-5-10 mg/kg ip of sertraline and 10-20-40 mg/kg ip of spironolactone are not effective in reducing tolerance caused by morphine. Therefore, we need more studies about the possible mechanisms in the mentioned injection amounts of sertraline and spironolactone drugs.