Effects of Vitamin B6 on the Expression and Development of Tolerance to Morphine Stimulating Effects on Locomotor Activity in Mice

Chronic use of morphine may induce tolerance to its different pharmacological effects. Vitamin B6 has a central role, as a cofactor, in the biosynthesis of neurotransmitters that are involve in morphine's effects. Moreover, this vitamin affects on morphine's reward and analgesic properties. Therefore, the current research aimed to evaluate the effects of vitamin B6 on the expression and acquisition of tolerance to morphine locomotor-stimulating effects.Twenty groups of mice (n=8) were selected randomly. Acute effects of different doses of morphine (1-30 mg/kg) or vitamin B6 (25-75 mg/kg) on locomotor activity were evaluated using an activity meter. Induction of tolerance was conducted using morphine (30 mg/kg)×2 times a day×3 days plus a single dose of morphine (30 mg/kg) on fourth day. In expression experiment, vitamin B6 (25-75 mg/kg) or saline was injected one hour before the last dose morphine, after tolerance induction. In the acquisition test, one hour before each dose of morphine (in the first three days of tolerance induction) saline or vitamin B6 (25-75 mg/kg) was administered to mice.Although vitamin B6 had no effect on locomotion, administration of morphine had a biphasic effect on mice's locomotor activity; it decreased locomotion at a low dose (5 mg/kg) and increased it at a high dose (30 mg/kg). Furthermore, administration of vitamin B6 before morphine could inhibit the expression and the acquisition of tolerance to morphine-stimulating effects on locomotor activity.Vitamin B6 may be considered as a nutritional supplement in reducing morphine tolerance.