Boman Lindsey, De Butte Maxine
Department of Psychology, Sociology, and Social Work, West Texas A&M University, Canyon, TX, USA.
Department of Psychology, Sociology, and Social Work, West Texas A&M University, Canyon, TX, USA.
Behav Brain Res. 2019 May 2;363:155-160. doi: 10.1016/j.bbr.2019.02.009. Epub 2019 Feb 5.
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.
尽管用于治疗儿童各种精神疾病的抗精神病药物使用量大幅增加，但关于早期治疗的长期影响的文献却很匮乏。一些研究表明，早期用药会导致神经传递系统发生不同的改变，但很少有研究调查是否存在长期的行为改变。因此，本研究的目的是使用幼年大鼠来研究低剂量利培酮（一种常用的抗精神病药物）治疗的神经行为效应。将24只雄性斯普拉格-道利大鼠皮下植入持续释放的利培酮微丸（0.04毫克/天）或安慰剂微丸。为了涵盖对大脑发育至关重要的围青春期到青春期时间段（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。利培酮治疗开始六周后，所有大鼠都接受了一系列行为评估测试，包括旷场试验、物体识别试验、莫里斯水迷宫试验和Y迷宫试验。利培酮治疗对旷场试验、物体识别试验或莫里斯水迷宫试验的表现没有影响。在Y迷宫试验中发现了显著影响。尽管所有大鼠都表现出正常的自发交替，但接受利培酮治疗的大鼠表现出明显更高的同臂返回率，这表明存在工作记忆缺陷。需要继续进行研究以确定早期接触利培酮是否会在更长时间点导致工作记忆方面的差异。这些结果似乎表明，在围青春期和青春期期间早期低剂量利培酮治疗不会严重损害行为。
