Objective: Isoniazid, is a synthetic antibiotic that has been used for long periods of time, as a safe drug, in the treatment of tuberculosis. This drug can easily penetrate the nervous system where it can modulate the GABAergic systems of the brain. Because GABA has an important role in morphine-induced reward, the purpose of the present study was to evaluate the effects of isoniazid on the acquisition of morphine-induced conditioned place preference (CPP) in mice. Methods: a biased conditioned place preference method (as a known method for assessment of rewarding effects of drugs) was used to evaluate possible rewarding effects of drugs in female NMRI mice. In the first step, the effects of morphine and isoniazid on the induction of place conditioning were evaluated. In the next step, different doses of isoniazid were injected before injection of morphine effective dose, in conditioning days, to evaluate the possible effects of isoniazid on the acquisition of morphine CPP. Results: morphine administration in different doses (0.5, 1, 2, 5 and 10 mg/kg) induced conditioned place preference in the animals. However, isoniazid injection (25.50 and 75 mg/kg) by itself, in the conditioning days, could not induce any place preference or aversion. On the other hand, administration of isoniazid (25.50 and 75 mg/kg) before the effective dose of morphine (5 mg/kg) decreased the acquisition of morphine-induced conditioned place preference, significantly (p<0.01). Conclusion: It can be concluded that isoniazid may interact with the rewarding effects of morphine.
