Risperidone use in children and adolescents is associated with the development of metabolic disorders including increased accumulation of body fat, dyslipidemia, and glucose and insulin metabolism dysregulation. As pharmacological interventions are often limited in their ability to treat a range of side-effects, this study aimed to evaluate the effectiveness of daily voluntary exercise intervention to prevent metabolic side-effects induced by risperidone in juveniles. Thirty-two juvenile female Sprague Dawley rats were treated with risperidone (0.9 mg/kg; b.i.d; n = 16) or vehicle (0.3 g cookie dough pellet; n = 16). These rats were then assigned to a sedentary or voluntary exercise intervention (three hours daily access to running wheels) group (n = 8/group) for a period of four weeks. An intra-peritoneal glucose tolerance test was performed after three weeks of risperidone treatment and exercise intervention to assess glucose tolerance. During the exercise intervention, risperidone-treated rats ran significantly less than vehicle-treated rats. Risperidone treatment of sedentary rats resulted in significantly increased white adipose tissue, fasting triglyceride and fasting insulin compared to vehicle-treated sedentary rats. Exercise intervention of risperidone-treated rats prevented significant increases in these metabolic parameters compared to risperidone-treated sedentary rats. These results support voluntary exercise as an effective mitigator of metabolic side-effects associated with risperidone treatment in juvenile rats. Dyslipidemia and dysregulation of glucose and insulin metabolism are significant risk factors for morbidities and mortality later in life, therefore a focus on strategies to mitigate these adverse effects is critical. Our findings support clinical trials in exercise intervention to prevent metabolic disorders associated with antipsychotic medication in children and adolescents.

在儿童和青少年中使用利培酮与新陈代谢紊乱有关，包括增加体内脂肪积累，血脂异常以及葡萄糖和胰岛素代谢失调。由于药理学干预措施通常不能有效治疗多种副作用，因此本研究旨在评估每日自愿运动干预措施以预防利培酮在青少年中引起的代谢副作用的有效性。用利培酮（0.9 mg / kg；bid；n  = 16）或媒介物（0.3 g曲奇面团团； n = 16）对32只Sprague Dawley雌性幼鼠进行治疗。然后将这些大鼠分配到久坐或自愿运动干预组（每天三个小时使用车轮）（n = 8 /组），为期四个星期。利培酮治疗和运动干预三周后进行了腹膜内葡萄糖耐量测试，以评估葡萄糖耐量。在运动干预期间，使用利培酮治疗的大鼠的跑动明显少于使用载体治疗的大鼠。与载体治疗的久坐大鼠相比，利培酮治疗久坐大鼠的结果显着增加了白色脂肪组织，空腹甘油三酯和空腹胰岛素的含量。与利培酮治疗的久坐大鼠相比，利培酮治疗的大鼠的运动干预阻止了这些代谢参数的显着增加。这些结果支持自愿运动，作为与利培酮治疗有关的幼年大鼠代谢副作用的有效缓解剂。血脂异常以及葡萄糖和胰岛素代谢异常是生命后期发病和死亡的重要危险因素，因此，关注减轻这些不良影响的策略至关重要。我们的发现支持运动干预的临床试验，以预防与青少年抗精神病药物有关的代谢紊乱。