Neurobehavioral effects of chronic low-dose risperidone administration in juvenile male rats
Neurobehavioral effects of chronic low-dose risperidone administration in juvenile male rats
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DOI：
10.1016/j.bbr.2019.02.009
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发表时间：
2019-05-02
影响因子：
2.7
通讯作者：
De Butte, Maxine
中科院分区：
文献类型：
--
作者：
Boman, Lindsey;De Butte, Maxine
尽管使用抗精神病药物治疗儿童各种精神疾病的情况大幅增加，但缺乏关于早期治疗的长期影响的文献。一些研究表明，早期给药导致神经传递系统的差异性改变，但很少有研究调查是否有长期的行为改变。因此，本研究的目的是调查使用幼年大鼠的低剂量利培酮（一种常用的抗精神病药物）治疗的神经行为影响。24只雄性Sprague-Dawley大鼠皮下植入连续释放利培酮丸剂（0.04 mg/天）或安慰剂丸剂。为了涵盖被认为对大脑发育重要的围青春期至青春期时间段（出生后第40-70天），雄性大鼠在出生后第35天开始利培酮治疗。在利培酮治疗开始后6周，对所有大鼠进行一系列行为评估，包括旷场、物体识别、Morris水迷宫和Y-迷宫任务。利培酮治疗不影响在旷场、物体识别或Morris水迷宫上的表现。在Y-迷宫上发现了显著的效果。尽管所有大鼠均表现出正常的自发交替，但利培酮治疗的大鼠表现出显著更高的同臂返回，表明工作记忆缺陷。需要继续研究，以确定是否早期暴露于利培酮可能会导致工作记忆在较长的时间点的差异。这些结果似乎表明，在围青春期和青春期早期低剂量利培酮治疗不会严重损害行为。
Despite substantial increases in the use of antipsychotics to treat various psychiatric conditions in children, there is a lack of literature regarding long-term effects of early treatment. Some studies have indicated that early administration results in differential alterations to neurotransmission systems, but few studies have investigated whether there are long-term behavioral modifications. Therefore, the aim of the current study was to investigate the neurobehavioral effects of low dose risperidone (a commonly prescribed antipsychotic) treatment using juvenile rats. Twenty-four male Sprague-Dawley rats were either subcutaneously implanted with a continuous release risperidone pellet (.04 mg/day) or a placebo pellet. To encompass the peri-adolescent to adolescent timeframe (postnatal day 40-70) thought to be important for brain development, male rats began risperidone treatment at post-natal day 35. Six weeks following commencement of risperidone treatment, all rats were tested on a battery of behavioral assessments including open field, object recognition, Morris Water Maze, and Y-Maze tasks. Risperidone treatment did not affect performance on the open field, object recognition, or Morris Water maze. A significant effect was found on the Y-maze. Although all rats exhibited normal spontaneous alternation, risperidone treated rats demonstrated significantly higher same arm returns, indicative of a working memory deficit. Continued research is needed to determine whether early exposure to risperidone may lead to differences in working memory at longer time-points. These results seem to indicate that early low dose risperidone treatment during the peri-adolescent and adolescent period does not severely impair behavior.