Introduction: Morphine, which is an important opioid drug in medical centers, especially is used for the treatment of moderate to severe pain. In addition to pain relief, morphine also has euphoric effects that may lead to its abuse for recreational purposes. One side effects of morphine use for long times is tolerance. Tolerance to euphoric effects of morphine makes dependent peoples take higher doses of the drug for experiencing the previous euphoria. Isoniazid is a chemotherapy agent that is prescribed for the treatment of tuberculosis. This drug has the ability to penetrate the brain and to affect the GABAergic systems. Previous research has shown that GABAergic agents have important effects on morphine euphoric or rewarding properties. Therefore, the aim of the present study was to evaluate the effects of isoniazid on tolerance to euphoric effects of morphine. Methods: conditioned place preference paradigm was used for evaluation of morphine or isoniazid reward or euphoria in female mice. For induction of tolerance to morphine, high doses of morphine (50 mg/kg) was injected, subcutaneously, twice daily for four consecutive days. In these days, before each morphine injection, saline or different doses of isoniazid (25, 50 and 75 mg/kg) was injected, intraperitoneally. Results: Morphine (0.5-10 mg/kg), alone, could induce a significant place preference. Isoniazid by itself induced no place preference or aversion. Administration of different doses of isoniazid before morphine inhibited the induction of tolerance to euphoric effects of morphine by morphine high doses. Conclusion: Since isoniazid is a safe drug, it also may be useful in the treatment of side effects of opioid uses such as tolerance.
