Background and Objective: Repeated use of morphine may lead to dependence on the drug. Abrupt cessation of morphine administration in morphine-dependent persons can induce withdrawal signs that are an obstacle for morphine addiction treatment. Finding new drugs that can prevent or alleviate the withdrawal signs of morphine may be helpful for prevention of relapse to morphine abuse. Previous research has shown that GABAergic brain systems might alter morphine-withdrawal signs; therefore, the present investigation was conducted to evaluate the effects of modulation of GABAergic systems of brain by isoniazid on naloxone-induced withdrawal signs in morphine-dependent male mice. Materials and Methods: Mice rendered dependent on morphine by the administration of 10 high doses of morphine on four days: nine doses of morphine (50, 50 and 75 mg/kg, s.c.)× 3 days and a single morphine dose (50 mg/kg, s.c.) on the fourth day. For evaluation of isoniazid effects on the acquisition of morphine dependence, four groups of animals received saline or isoniazid (25, 50 and 75 mg/kg, i.p.) before administration of the high doses of morphine for dependence induction. On the test day, two hours after the last morphine dose, all the animals received naloxone (5mg/kg, i.p.). Results: Isoniazid administration before morphine could reduce the naloxone-precipitated withdrawal signs (Jumping, rearing, and diarrhea) in morphine-dependent mice, significantly. Conclusion: Isoniazid may be a good candidate for the prevention of morphine withdrawal syndrome.
