A New Look at an Old Drug: Cumulative Effects of Low Ribavirin Doses in Amphetamine-Sensitized Rats

Abstract

Background: Psychotic states related to psychostimulant misuse in patients with hepatitis C virus infection may complicate acceptance and reaction to antiviral treatment. This observation equally applies to widely used ribavirin therapy. Objective: We examined psychomotor and body weight gain response to low ribavirin doses after cessation of intermittent amphetamine treatment in adult rats to assess its role in neurobehavioral outcome during psychostimulant withdrawal. Method: The model of amphetamine-induced (1.5 mg/kg/day, i.p., 7 consecutive days) motor sensitization and affected body weight gain was established in adult male Wistar rats. Then, additional cohort of amphetamine-sensitized rats was subjected to saline (0.9% NaCl; 1 mL/kg/day; i.p.) or ribavirin (10, 20 and 30 mg/kg/day, i.p.) treatment for 7 consecutive days. Animals’ motor activity in a novel environment was monitored after the 1st and the 7th saline/ribavirin injection. Body weight gain was calculated as appropriate. Determination and quantification of ribavirin in the brain tissue were performed too. Results: The 1st application of ribavirin to amphetamine-sensitized rats affected/decreased their novelty-induced motor activity only at a dose of 30 mg/kg. After the 7th application, ribavirin 30 mg/kg/day still decreased while 10 and 20 mg/kg/day increased novelty-induced motor activity. These behavioral effects coincided with the time required to reach maximum ribavirin concentration in the brain. Body weight gain during withdrawal was not influenced by any of the doses tested. Conclusion: Ribavirin displays central effects that in repeated treatment, depending on the applied dose, could significantly influence psychomotor response but not body weight gain during psychostimulant/amphetamine withdrawal.