Evaluation of the effect of L- carnitine and Ketotifen on Morphine induced dependence in mice

Abstract

Introduction:the opioid system is affected by different neurotransmitter systems (such as Glutamatergic, Adrenergic, Histaminergic systems) and oxidative stress reactions. Result from Pervious studies have shown a positive effect on inhibition of the Glutamatergic system. Goal: The effect of Ketotifen and L- Carnitine on the prevention of withdrawal syndrome caused by morphine, has investigated in the current study. Method: nine groups containing 8 male mice, weighing between 20-30 grams are chosen randomly and get medication mentioned below once daily for four days: 1) Saline (10mg/kg,i.p.) + Saline (10mg/kg,i.p.) 2) Morphine (50mg/kg,i.p.) + Saline (10mg/kg,i.p.) 3,4,5) Morphine (50mg/kg,i.p.) + Ketotifen (4,8,16mg/kg,i.p.) 6,7,8) Morphine (50mg/kg,i.p.) + L- carnitine (25,50,75mg/kg,i.p.) 9) Morphine (50mg/kg,i.p.) + L- carnitine (25mg/kg,i.p.) + Ketotifen (4mg/kg,i.p.) To evaluate the effect of medications on morphine dependency, in day 4, 2 hours after the last morphine dose, the researcher give them a shot of Naloxone (4mg/kg,i.p.) and records withdrawal symptoms of each mouse (jumping and standing on two feet) for half an hour. In the end in order to study the efficacy of medications on oxidative stress system, the researcher prepares blood samples extracted from the heart of animals and runs the oxidative stress biomarkers (MDA and TAC) tests. Results: The injection of Ketotifen and L- carnitine, separately and in combination with each other (in low dosages), before the daily injection of morphine, revealed, this drugs reduced morphine dependence in mice. Conclusion: According to results obtained, it can be concluded that Ketotifen on L- carnitine can be used to reduce morphine dependency.