Intermittent treatment with haloperidol or quetiapine does not disrupt motor and cognitive recovery after experimental brain trauma.
Intermittent treatment with haloperidol or quetiapine does not disrupt motor and cognitive recovery after experimental brain trauma.
复制标题
氟哌啶醇或喹硫平的间歇治疗不会扰乱实验性脑损伤后的运动和认知恢复。
DOI：
10.1016/j.bbr.2016.09.049
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发表时间：
2018
影响因子：
2.7
通讯作者：
Kline,AnthonyE
中科院分区：
文献类型：
--
作者：
Weeks,JillianJ;Carlson,LaurenJ;Radabaugh,HannahL;delaTremblaye,PatriciaB;Bondi,CorinaO;Kline,AnthonyE
创伤性脑损伤(TBI)引起的激动和攻击对急诊医院和康复环境中的临床医生构成了主要障碍。因此，对这些症状的管理至关重要。抗精神病药物(APD)是缓解这些症状的常见治疗方法。然而，先前的临床前脑损伤研究表明，每天和长期服用这些药物(如氟哌啶醇；HAL)会加剧认知和运动障碍。奎硫平(quetiapine，QUE)是一种非典型的APD，与许多典型的APD(如HAL)不同，它与D2受体的解离速度相对较快。本研究的目的是验证以下假设：间歇性HAL和QUE不会阻碍脑外伤后认知和运动功能的恢复，每天QUE也不会损害功能恢复，这与HAL相反。70只麻醉雄性大鼠接受控制性皮质撞击或假损伤，然后随机分为脑创伤组和假手术组，分别给予HAL(0.5 mg/kg)或Que(10 mg/kg)，每天一次或隔日一次，并与各自和赋形剂(VEH)对照组进行比较。术后第1~5天用平衡木平衡/行走测试评定运动功能，第14~19天用Morris水迷宫评定认知功能。假手术组之间在任何任务上均无差异，因此将数据汇总。无论治疗或管理模式如何，脑损伤组之间没有发现总体差异，但与假对照组相比，所有组都受到了损害[P<；P<；0.05]。假对照组在认知测试中的表现也明显好于所有的脑损伤组[p<；n0.05]。此外，脑损伤+持续HAL组的表现比脑损伤+持续VEH组、脑损伤+持续QUE组和脑损伤+间歇性QUE组差，差异无统计学意义[P<；0.05]。总体而言，数据表明QUE不会加剧脑外伤引起的认知和运动障碍，这支持了这一假说。QUE可能会被证明是治疗临床脑外伤后激越和攻击性的一种替代的雪崩疗法。哈尔也可能是安全的，但只有在谨慎使用的情况下。
Traumatic brain injury (TBI)-induced agitation and aggression pose major obstacles to clinicians in the acute hospital and rehabilitation settings. Thus, management of these symptoms is crucial. Antipsychotic drugs (APDs) are a common treatment approach for alleviating these symptoms. However, previous preclinical TBI studies have indicated that daily and chronic administration of these drugs (e.g., haloperidol; HAL) can exacerbate cognitive and motor deficits. Quetiapine (QUE) is an atypical APD that differs from many typical APDs, such as HAL, in its relatively rapid dissociation from the D2receptor. The goal of this study was to test the hypotheses that intermittent HAL and QUE would not hinder recovery of cognitive and motor function following TBI and that daily QUE would also not impair functional recovery, which would be in contrast to HAL. Seventy anesthetized male rats received either a controlled cortical impact or sham injury and were then randomly assigned to TBI and sham groups receiving HAL (0.5 mg/kg) or QUE (10 mg/kg) intraperitoneally once per day or once every other day and compared to each other and vehicle (VEH) controls. Motor function was assessed by beam balance/walk tests on post-operative days 1–5 and cognitive function was evaluated with a Morris water maze task on days 14–19. No differences were revealed among the sham groups in any task, and hence the data were pooled. No overall differences were detected among the TBI groups, regardless of treatment or administration paradigm [p> 0.05], but all were impaired vs. SHAM controls [p< 0.05]. The SHAM controls also performed significantly better in the cognitive test vs. all TBI groups [p< 0.05]. Moreover, the TBI + continuous HAL group performed worse than the TBI + continuous VEH, TBI + continuous QUE, and TBI + intermittent QUE groups [p< 0.05], which did not differ from one another. Overall, the data suggest that QUE does not exacerbate TBI-induced cognitive and motor deficits, which supports the hypothesis. QUE may prove useful as an alternative APD treatment for management of agitation and aggression after clinical TBI. HAL may also be safe, but only if used sparingly.