Effects of Isoniazid on the Acquisition and Expression of Morphine Dependence in Male Mice

Background: GABAergic drugs have extensive interference with morphine’s pharmacological effects, including dependence.  Objectives: The present study was conducted to evaluate the effects of isoniazid, a GABAergic agent, on the acquisition and expression of morphine-induced dependence in male mice. Methods: Sixty-four male mice were used. The mice became dependent on morphine by administrating ten doses of morphine in four days. For the precipitation of the morphine withdrawal signs (jumping, diarrhea, and weight loss), two hours after the last dose of morphine, the mice received naloxone (۴ mg/kg, IP). In the expression experiment, four groups of mice received saline or isoniazid (۲۵, ۵۰, and ۷۵ mg/kg, IP) one hour before naloxone. In the acquisition experiment, the other four groups, one hour before the first six doses of morphine, received saline or isoniazid (۲۵, ۵۰, and ۷۵ mg/kg, IP).  Results: In the expression experiment, all doses of isoniazid decreased the number of jumping in mice, but only the lowest dose influenced diarrhea (increased weight of diarrheal stool) significantly. The higher doses of isoniazid (۵۰ and ۷۵ mg/kg, IP) caused a significant reduction in the percentage of weight loss, but its lowest dose (۲۵ mg/kg, IP) significantly increased the sign. In the acquisition experiment, isoniazid (۲۵, ۵۰ mg/kg IP) decreased the number of jumping and the percentage of weight loss, but not the weight of diarrheal stool. Conclusion: Isoniazid may be a good candidate to prevent morphine withdrawal signs.

Keywords:

Isoniazid , Morphine dependence , Naloxone , Substance withdrawal syndrome , Mice