Department of Neurophysiology, Institute for Biological Research "Siniša Stanković" - National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia.
Institute for Research and Development, Galenika a.d., Belgrade, Serbia.
Curr Pharm Des. 2020;26(31):3884-3894. doi: 10.2174/1381612826666200326125821.
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 the widely used ribavirin therapy.
We examined psychomotor and body weight gain responses to low ribavirin doses after cessation of intermittent amphetamine treatment in adult rats to assess its role in neurobehavioral outcome during psychostimulant withdrawal.
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 amphetaminesensitized 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 also.
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.
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.
丙型肝炎病毒感染患者因滥用精神兴奋剂而导致的精神病状态可能会影响其对抗病毒治疗的接受程度和反应。这种观察同样适用于广泛使用的利巴韦林治疗。
我们研究了在成年大鼠停止间歇性安非他命治疗后，低剂量利巴韦林对精神兴奋剂戒断期间神经行为结果的影响。
在成年雄性 Wistar 大鼠中建立了安非他命诱导的（1.5mg/kg/天，腹腔注射，连续 7 天）运动敏化和体重增加受影响的模型。然后，另一组安非他命敏化大鼠接受生理盐水（0.9%NaCl；1mL/kg/天，腹腔注射）或利巴韦林（10、20 和 30mg/kg/天，腹腔注射）连续 7 天治疗。在第 1 次和第 7 次生理盐水/利巴韦林注射后监测动物在新环境中的运动活动。按适当方法计算体重增加。还进行了脑组织中利巴韦林的测定和定量。
第 1 次给予利巴韦林至安非他命敏化大鼠，仅在 30mg/kg 剂量下影响/降低了它们对新奇环境的运动活性。第 7 次给药后，30mg/kg/天的利巴韦林仍可降低运动活性，而 10 和 20mg/kg/天则可增加新奇环境下的运动活性。这些行为效应与达到大脑中利巴韦林最大浓度所需的时间一致。在停药期间，体重增加不受任何测试剂量的影响。
利巴韦林具有中枢作用，在重复治疗中，根据应用剂量，可能会显著影响精神兴奋剂/安非他命戒断期间的精神运动反应，但不影响体重增加。
