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Cariprazine alleviates core behavioral deficits in the prenatal valproic acid exposure model of autism spectrum disorder
Psychopharmacology ( IF 3.4 ) Pub Date : 2021-07-15 , DOI: 10.1007/s00213-021-05851-6
Viktor Román 1 , Nika Adham 2 , Andrew G Foley 3 , Lynsey Hanratty 3 , Bence Farkas 1 , Balázs Lendvai 1 , Béla Kiss 1
Affiliation  

Rationale

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction and restricted, repetitive behaviors. The unmet medical need in ASD is considerable since there is no approved pharmacotherapy for the treatment of these deficits in social communication, interaction, and behavior. Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist, is already approved for the treatment of schizophrenia and bipolar I disorder in adults; investigation in patients with ASD is warranted.

Objectives

The aim of this study was to investigate the effects of cariprazine, compared with risperidone and aripiprazole, in the rat prenatal valporic acid (VPA) exposure model on behavioral endpoints representing the core and associated symptoms of ASD.

Methods

To induce the ASD model, time-mated Wistar rat dams were treated with VPA during pregnancy. Male offspring were assigned to groups and studied in a behavioral test battery at different ages, employing social play, open field, social approach-avoidance, and social recognition memory tests. Animals were dosed orally, once a day for 8 days, with test compounds (cariprazine, risperidone, aripiprazole) or vehicle before behavioral assessment.

Results

Cariprazine showed dose-dependent efficacy on all behavioral endpoints. In the social play paradigm, only cariprazine was effective. On the remaining behavioral endpoints, including the reversal of hyperactivity, risperidone and aripiprazole displayed similar efficacy to cariprazine.

Conclusions

In the present study, cariprazine effectively reversed core behavioral deficits and hyperactivity present in juvenile and young adult autistic-like rats. These findings indicate that cariprazine may be useful in the treatment of ASD symptoms.



中文翻译:

Cariprazine 减轻自闭症谱系障碍产前丙戊酸暴露模型中的核心行为缺陷

基本原理

自闭症谱系障碍 (ASD) 是一种神经发育疾病,其特征是社交沟通和互动缺陷以及受限、重复的行为。ASD 中未满足的医疗需求是相当大的,因为没有批准的药物疗法来治疗这些社会交流、互动和行为方面的缺陷。Cariprazine 是一种多巴胺 D 3偏好的D 3 /D 2受体部分激动剂,已被批准用于治疗成人精神分裂症和双相 I 型障碍;有必要对 ASD 患者进行调查。

目标

本研究的目的是在大鼠产前丙戊酸 (VPA) 暴露模型中研究卡利拉嗪与利培酮和阿立哌唑相比对代表 ASD 核心和相关症状的行为终点的影响。

方法

为了诱导 ASD 模型,时间交配的 Wistar 大鼠水坝在怀孕期间用 VPA 治疗。雄性后代被分组并在不同年龄的行为测试组中进行研究,采用社交游戏、开放领域、避免社交接近和社交识别记忆测试。在行为评估之前,每天一次给动物口服给药试验化合物(卡利拉嗪、利培酮、阿立哌唑)或载体,持续 8 天。

结果

Cariprazine 在所有行为终点上均显示出剂量依赖性疗效。在社交游戏范式中,只有卡利拉嗪有效。在其余的行为终点,包括多动的逆转,利培酮和阿立哌唑显示出与卡利拉嗪相似的功效。

结论

在本研究中,cariprazine 有效地逆转了幼年和年轻成年自闭症样大鼠的核心行为缺陷和多动症。这些发现表明,卡利拉嗪可能有助于治疗 ASD 症状。

更新日期:2021-07-15
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