Chronic Atypical Neuroleptic Treatment

描述（由申请人提供）：非典型的精神抑制药，如利培酮和奎替利钠，经常用于患有严重精神病理学的儿童和青少年。 这些药物对正常生长和发育的影响目前尚不清楚。 该项目将对48只正常发育的13-24个月龄的幼年猪尾猴（Macaca nemestrina）进行利培酮、奎替利酮或安慰剂治疗，并将研究4个月的用药后阶段。 一岁的猴子在身体成熟、运动技能、生理学和物种寿命中达到的比例方面与4岁的儿童发育相似。 12名男性将接受低剂量的利培酮或奎替鲁治疗4个月，然后每个药物组中的8名将转换为高剂量治疗4个月。 将24只雄性动物分配至安慰剂组。 在药物或安慰剂治疗前、治疗期间和治疗后，对动物进行（1）社交、情感、探索、学习和记忆、运动技能和感知行为;以及（2）健康、躯体生长、骨矿化、免疫系统状态和激素功能的身体评估。 研究设计将允许组间和个体内比较，以检查药物组差异以及药物引起的个体生长率变化。 由于猪尾猴表现出与人类相当的心理和身体发育，该项目将确定人类儿童的发育方面可能受到这些药物长期治疗的影响。

DESCRIPTION (provided by applicant): Atypical neuroleptics such as risperidone and quetiapine are being used frequently in children and adolescents with severe psychopathology. The effects of these agents on normal growth and development are currently unknown. This project will treat 48 normally developing young pigtail monkeys (Macaca nemestrina) with risperidone, quetiapine, or placebo from 13-24 months of age, and will study a four-month post-drug period. Monkeys at one year of age are developmentally similar to children at 4 years of age in physical maturation, motor skills, physiology, and proportion reached in the species lifespan. Twelve males will receive a low dose of risperidone or quetiapine for 4 months, and then 8 in each drug group will be switched to a high dose for 4 months. Twenty-four males will be assigned to the placebo condition. Animals will be tested before, during, and after drug or placebo treatment for (1) social, emotional, exploratory, learning and memory, motor skill, and perceptual behavior; and (2) physical assessments of health, somatic growth, bone mineralization, immune system status, and hormonal function. The study design will permit both between-group and within-individual comparisons to examine drug group differences as well as alterations in individual growth rates caused by the drugs. Since pigtail monkeys demonstrate psychological and somatic development comparable to humans, this project will identify aspects of development in human children that are likely to be affected by chronic treatment with these agents.