Bardgett Mark E, Crane Casey, Baltes Thompson Emily C, Cox Bethanie, Downnen Tyler
Department of Psychological Science, Northern Kentucky University, Highland Heights, KY 41076, United States.
Department of Psychological Science, Northern Kentucky University, Highland Heights, KY 41076, United States.
Behav Brain Res. 2019 Apr 19;362:64-70. doi: 10.1016/j.bbr.2018.12.044. Epub 2018 Dec 27.
Antipsychotic drugs are used to manage symptoms of pediatric psychiatric disorders despite the relative absence of research regarding the long-term effects of these drugs on brain development. Using rats as a model, research has demonstrated that administration of the antipsychotic drug, risperidone, during early postnatal development elevates locomotor activity and sensitivity to the locomotor effects of amphetamine during adulthood. Because risperidone targets neurotransmitter receptors and forebrain regions associated with working memory, the present study determined whether early-life risperidone altered working memory during adulthood and its sensitivity to amphetamine-induced impairment. Female and male rats received subcutaneous (sc) injections of risperidone daily on postnatal days 14-42. Early-life risperidone increased spontaneous locomotor activity and amphetamine-induced hyperactivity during adulthood, although the effects were significantly greater in females. Working memory was tested in an operant-based, delayed non-matching-to-sample task. Early-life risperidone did not affect the percentage of correct choices observed during sessions with 0-8 second delays but impaired performance during sessions with 0-24 second delays. In a subsequent set of tests using 0-24 second delays, amphetamine (0.75 and 1.25 mg/kg, sc) significantly reduced the percentage of correct choices at most delays, but risperidone did not exacerbate this effect. These data suggest that early-life risperidone leads to modest deficits in working memory during adulthood, but does not alter the perturbation of working memory by amphetamine.
尽管关于抗精神病药物对儿童大脑发育的长期影响的研究相对较少，但这些药物仍被用于治疗儿童精神疾病的症状。以大鼠为模型的研究表明，在出生后早期发育阶段给予抗精神病药物利培酮，会提高成年期的运动活动以及对苯丙胺运动效应的敏感性。由于利培酮作用于与工作记忆相关的神经递质受体和前脑区域，本研究确定了生命早期接触利培酮是否会改变成年期的工作记忆及其对苯丙胺诱导损伤的敏感性。雌性和雄性大鼠在出生后第14至42天每天接受皮下注射利培酮。生命早期接触利培酮会增加成年期的自发运动活动和苯丙胺诱导的多动，尽管雌性大鼠的这种影响明显更大。在基于操作性的延迟非匹配样本任务中测试工作记忆。生命早期接触利培酮对0至8秒延迟的实验中正确选择的百分比没有影响，但在0至24秒延迟的实验中损害了表现。在随后一组使用0至24秒延迟的测试中，苯丙胺（0.75和1.25mg/kg，皮下注射）在大多数延迟情况下显著降低了正确选择的百分比，但利培酮并没有加剧这种影响。这些数据表明，生命早期接触利培酮会导致成年期工作记忆出现适度缺陷，但不会改变苯丙胺对工作记忆的干扰。
