Prevention of morphine dependence with a combination of ketotifen and l-carnitine in mice: a new potential therapeutic approach.

Morphine dependence is a complex clinical issue, coinciding with oxidative stress and increased neurotransmitter levels as key factors in this drug's reliance and tolerance. This study examines how l-carnitine, ketotifen, and their combination prevent and treat morphine dependence in mice. Seventy-two male mice (20-25 g) were randomly divided into nine groups. The morphine group received morphine (50 mg/kg/i.p.) for 4 days, while the control group was given saline (10 ml/kg/i.p.). After the morphine administration, three groups received l-carnitine at doses of 25, 50, and 75 mg/kg/i.p., and the following three groups received ketotifen at doses of 4, 8, and 16 mg/kg/i.p. The final group was treated with l-carnitine (25 mg/kg/i.p.) and ketotifen (4 mg/kg/i.p.) after the morphine administration. The morphine dependence was assessed using the jumping and standing on feet indices in the naloxone test. Oxidative stress was evaluated through total antioxidant capacity (TAC) and malondialdehyde (MDA) biomarkers in blood samples. l-carnitine (25, 50, and 75 mg/kg) and ketotifen (4, 8, and 16 mg/kg) reduced the naloxone jumping index. l-carnitine (50 mg/kg) and ketotifen (8 and 16 mg/kg) reduced the standing on feet index. In addition, combining these two medications at modest doses decreased behavioral indices. All three l-carnitine doses and two ketotifen doses lowered MDA and increased TAC. Treating with ketotifen at 4 mg/kg was ineffective; however, when combined with l-carnitine (25 mg/kg), it provided antioxidant benefits. Ketotifen and l-carnitine, by affecting the oxidative stress pathway, reduce the symptoms of morphine dependence and act as potential pharmacological treatments for this condition.