Exercise intervention for preventing risperidone-induced dyslipidemia and gluco-metabolic disorders in female juvenile rats

Abstract

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.

Keywords: Adipose tissue; Antipsychotic drug; Dyslipidemia; Exercise; Glucose tolerance test; Insulin resistance.