Isoniazid, a hydrazine derivative, can influence the GABAergic system, which plays an important role in modulating morphine tolerance. This study aimed to assess how isoniazid effects on both the expression and acquisition of tolerance to morphine-induced hyperlocomotion in mice. Nineteen groups of male mice (n=8 per group) were used. The locomotor activity of the animals was measured for a duration of 20 minutes using an actimeter after administration of morphine (1-30 mg/kg, s.c.) or isoniazid (25-75 mg/kg, i.p.). Tolerance was induced by administering morphine (30 mg/kg) twice daily for three consecutive days. The same dose on the fourth day served as a challenge to assess tolerance development. To investigate how isoniazid affects tolerance expression and acquisition, mice were divided into eight groups. Four groups received saline or isoniazid one hour before the final morphine dose (expression test). The remaining four groups were administered isoniazid prior to each morphine injection during the tolerance induction phase (acquisition test). Morphine produced two distinct effects on locomotor activity: at a low dose (1 mg/kg, s.c.) it reduced locomotion in mice (P<0.05), while at a high dose (30 mg/kg, s.c.) it increased locomotor activity (P<0.01). Isoniazid administration one hour before the test significantly increased locomotor activity. Isoniazid administration before morphine suppressed both the expression (P<0.01) and the acquisition (P<0.01) of morphine-induced hyperlocomotion. However, isoniazid’s effect on tolerance expression may be due to its ability to increase locomotor activity. Isoniazid could be a promising candidate for attenuating morphine tolerance development.
