Early antipsychotic treatment in childhood/adolescent period has long-term effects on depressive-like, anxiety-like and locomotor behaviours in adult rats
Early antipsychotic treatment in childhood/adolescent period has long-term effects on depressive-like, anxiety-like and locomotor behaviours in adult rats
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DOI：
10.1177/0269881115616383
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发表时间：
2016-02-01
影响因子：
4.1
通讯作者：
Deng, Chao
中科院分区：
文献类型：
--
作者：
De Santis, Michael;Lian, Jiamei;Deng, Chao
尽管对早期 APD 治疗的长期影响了解有限，但全世界儿童/青少年抗精神病药物 (APD) 的使用呈指数级增长。虽然研究发现早期治疗导致多巴胺和血清素神经传递系统发生一些改变（对于 APD 功效至关重要），但对潜在的长期行为变化的研究却很有限。这项研究使用儿童/青少年 APD 治疗动物模型，研究了阿立哌唑、奥氮平和利培酮对雄性和雌性大鼠成年行为的长期影响。然后在成年大鼠中进行旷场/洞板、高架十字迷宫（EPM）、社交互动和强迫游泳（FS）测试。我们的结果表明，在男性队列中，早期利培酮和奥氮平治疗引起了长期的过度运动效应（开放场/孔板和 FS 测试），同时观察到奥氮平治疗后抑郁样行为（在 FS 测试中）减少。此外，在旷场/孔板和 EPM 中测试对所有三种药物治疗的反应后，发现了类似抗焦虑的行为。然而，女性队列中的影响程度要小得多，早期利培酮和奥氮平治疗后的 FS 测试中表现出抑郁样行为增加和运动能力低下的行为特征。这些结果表明，不同的 APD 对成年大鼠的行为具有不同的长期影响。
Childhood/adolescent antipsychotic drug (APD) use is exponentially increasing worldwide, despite limited knowledge of the long-term effects of early APD treatment. Whilst investigations have found that early treatment has resulted in some alterations to dopamine and serotonin neurotransmission systems (essential to APD efficacy), there have only been limited studies into potential long-term behavioural changes. This study, using an animal model for childhood/adolescent APD treatment, investigated the long-term effects of aripiprazole, olanzapine and risperidone on adult behaviours of male and female rats. Open-field/holeboard, elevated plus maze (EPM), social interaction and forced swim (FS) tests were then conducted in adult rats. Our results indicated that in the male cohort, early risperidone and olanzapine treatment elicited long-term hyper-locomotor effects (open-field/holeboard and FS tests), whilst a decrease in depressive-like behaviour (in FS test) was observed in response to olanzapine treatment. Furthermore, anxiolytic-like behaviours were found following testing in the open-field/holeboard and EPM in response to all three drug treatments. Effects in the female cohort, however, were to a far lesser extent, with behavioural attributes indicative of an increased depressive-like behaviour and hypo-locomotor activity exhibited in the FS test following early risperidone and olanzapine treatment. These results suggest that various APDs have different long-term effects on the behaviours of adult rats.