Morphine is an important drug in medicine. Repeated administration of this opioid may cause tolerance to different actions, including locomotor-stimulating effect. The purpose of the current study was to evaluate the effects of isoniazid, as a GABAergic drug, on tolerance to morphine locomotor-stimulating effect in mice. Four groups of male mice (22-30 g) were used. Tolerance to the locomotor effect of morphine was induced by injection of morphine (30 mgikg, S.C., twice a day for 3 days). One h. before administration of each dose of morphine, one group (as control) received saline and the other three groups received isoniazid (25, 50, and 75 mgikg, i.p.). On the test day (day 4), a challenging dose of morphine (30 mg1g, S.C.) was injected into all of the mice. Administration of a high dose of morphine could induce tolerance to its locomotor activating effects, which was shown in control animals by reducing motor activity in animals that received a challenging dose of morphine (30 mgikg), on test day. Administration of isoniazid before morphine increased the locomotor activity of the animals after administration of the challenge dose of morphine on the test day (P<0.01). Isoniazid can inhibit the development of tolerance to the locomotor-enhancing effect of morphine.
