Adult Rats Treated With Risperidone During Development Are Hyperactive
Adult Rats Treated With Risperidone During Development Are Hyperactive
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DOI：
10.1037/a0031972
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发表时间：
2013-06-01
影响因子：
2.3
通讯作者：
Griffith, Molly S.
中科院分区：
文献类型：
--
作者：
Bardgett, Mark E.;Franks-Henry, Julie M.;Griffith, Molly S.
利培酮是一种批准用于儿童的抗精神病药物，但对利培酮早期治疗的长期影响知之甚少。在动物中，在发育过程中长期给予利培酮会在停止治疗后立即增加前脑多巴胺受体的表达。进行了一系列实验，以确定是否早期生活利培酮给药改变成年大鼠的自发活动，一种对多巴胺受体功能敏感的行为。另外一个由前脑多巴胺功能调节的行为，空间反转学习，也在成年期进行了测量。在每项研究中，Long-Evans大鼠从出生后第14天至第42天每天皮下注射溶剂或2种剂量的利培酮（1.0和3.0 mg/kg/天）中的1种。利培酮处理的大鼠在发育过程中体重增加轻微但显著减少。在前2个实验中，早期生命利培酮给药与给药后1周至约9个月龄的自发活动增加相关，与体重增加的变化无关。在一项单独的实验中，发现生命早期利培酮对雄性和雌性大鼠的自发活动具有增强作用。最后一项实验表明，在生命早期给予利培酮的成年大鼠中，空间反转学习不受影响。这些结果表明，在成年期的自发活动是永久性修改的早期生活利培酮治疗。研究结果表明，在儿科人群中长期使用抗精神病药物（e。例如，在一个实施例中，治疗自闭症的症状）可以改变大脑发育，改变成年期特定行为的神经设定点。
Risperidone is an antipsychotic drug approved for use in children, but little is known about the long-term effects of early-life risperidone treatment. In animals, prolonged risperidone administration during development increases forebrain dopamine receptor expression immediately upon the cessation of treatment. A series of experiments was performed to ascertain whether early-life risperidone administration altered locomotor activity, a behavior sensitive to dopamine receptor function, in adult rats. One additional behavior modulated by forebrain dopamine function, spatial reversal learning, was also measured during adulthood. In each study, Long-Evans rats received daily subcutaneous injections of vehicle or 1 of 2 doses of risperidone (1.0 and 3.0 mg/kg per day) from postnatal Days 14 to 42. Weight gain during development was slightly yet significantly reduced in risperidone-treated rats. In the first 2 experiments, early-life risperidone administration was associated with increased locomotor activity at 1 week postadministration through approximately 9 months of age, independent of changes in weight gain. In a separate experiment, it was found that the enhancing effect of early-life risperidone on locomotor activity occurred in males and female rats. A final experiment indicated that spatial reversal learning was unaffected in adult rats administered risperidone early in life. These results indicate that locomotor activity during adulthood is permanently modified by early-life risperidone treatment. The findings suggest that chronic antipsychotic drug use in pediatric populations (e. g., treatment for the symptoms of autism) could modify brain development and alter neural set points for specific behaviors during adulthood.