The effects of amphetamine on working memory and locomotor activity in adult rats administered risperidone early in life
The effects of amphetamine on working memory and locomotor activity in adult rats administered risperidone early in life
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DOI：
10.1016/j.bbr.2018.12.044
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发表时间：
2019-04-19
影响因子：
2.7
通讯作者：
Downnen，Tyler
中科院分区：
文献类型：
--
作者：
Bardgett，Mark E.;Crane，Casey;Downnen，Tyler
抗精神病药物被用来管理儿童精神障碍的症状，尽管相对缺乏关于这些药物对大脑发育的长期影响的研究。以大鼠为模型，研究表明，在出生后发育早期给予抗精神病药物利培酮，可以提高成年后运动活动和对苯丙胺运动效应的敏感度。因为利培酮针对的是神经递质受体和与工作记忆相关的前脑区域，所以本研究确定了早期利培酮是否改变了成年后的工作记忆，以及它对苯丙胺引起的损伤的敏感性。雌性和雄性大鼠在出生后14-42天每天皮下注射利培酮。早年的利培酮增加了成年后的自发活动和安非他明诱导的多动，尽管这种影响在女性中明显更大。工作记忆是在一个基于操作符的、延迟的、与样本不匹配的任务中测试的。早产儿利培酮不影响在0-8秒延迟的会话中观察到的正确选择的百分比，但在0-24秒延迟的会话中损害性能。在随后的一组使用0-24秒延迟的测试中，苯丙胺(0.75和1.25 mg/kg，sc)显著降低了大多数延迟的正确选择百分比，但利培酮并没有加剧这种影响。这些数据表明，生命早期的利培酮会导致成年后工作记忆的适度下降，但并不能改变安非他明对工作记忆的干扰。
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.