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Large nest building and high marble-burying: Two compulsive-like phenotypes expressed by deer mice (Peromyscus maniculatus bairdii) and their unique response to serotoninergic and dopamine modulating intervention.
Behavioural Brain Research ( IF 2.6 ) Pub Date : 2020-06-30 , DOI: 10.1016/j.bbr.2020.112794
Geoffrey de Brouwer 1 , Arina Fick 1 , Ané Lombaard 1 , Dan J Stein 2 , Brian H Harvey 3 , De Wet Wolmarans 1
Affiliation  

This study aimed to further dissect the deer mouse (Peromyscus maniculatus bairdii) model of compulsive-like behavior with respect to two persistent-like behavioral phenotypes viz. large nest building (LNB) and high marble-burying (HMB), which may be relevant to understanding the neurobiology of different symptom dimensions in obsessive-compulsive and related disorders. Since LNB is sensitive to chronic, high dose escitalopram intervention but HMB is not, we assessed whether the two behaviors could be further distinguished based on their response to 4 weeks of uninterrupted serotoninergic intervention (i.e. escitalopram; ESC; 50 mg/kg/day), dopaminergic antagonism, i.e. flupentixol; FLU; 0.9 mg/kg/day), dopaminergic potentiation (i.e. rasagiline; RAS; 5 mg/kg/day), and their respective combinations with escitalopram (ESC/FLU and ESC/RAS). Here we show LNB to be equally responsive to chronic ESC and ESC/FLU. HMB was insensitive to either of these interventions but was responsive to ESC/RAS. Additionally, we report that scoring preoccupied interaction with marbles over several trials is an appropriate measure of compulsive-like behavioral persistence in addition to the standard marble burying test. Taken together, these data provide further evidence that LNB and HMB in deer mice have distinctive neurobiological underpinnings. Thus, the naturally occurring compulsive-like behaviors expressed by deer mice may be useful in providing a platform to test unique treatment targets for different symptom dimensions of OCD and related disorders.



中文翻译:

大筑巢和高埋大理石:鹿鼠(Peromyscus maniculatus bairdii)表达的两种强迫样表型及其对血清素能和多巴胺调节干预的独特反应。

本研究旨在进一步剖析鹿鼠(Peromyscus maniculatus bairdii)的强迫性行为模型,涉及两种持久性行为表型,即。大型筑巢(LNB)和高位大理石埋葬(HMB),这可能与理解强迫症和相关疾病不同症状维度的神经生物学有关。由于 LNB 对慢性、高剂量依他普仑干预敏感,但 HMB 不敏感,我们评估了是否可以根据这两种行为对 4 周不间断血清素能干预(即依他普仑;ESC;50 毫克/公斤/天)的反应进一步区分,多巴胺能拮抗作用,即氟哌噻吨;流感; 0.9 毫克/公斤/天)、多巴胺能增强(即雷沙吉兰;RAS;5 毫克/公斤/天),以及它们各自与依他普仑的组合(ESC/FLU 和 ESC/RAS)。在这里,我们显示 LNB 对慢性 ESC 和 ESC/FLU 的反应相同。HMB 对这些干预中的任何一种都不敏感,但对 ESC/RAS 有反应。此外,我们报告说,除了标准的大理石埋葬测试之外,在几次试验中对与大理石的专注互动进行评分是一种适当的强迫性行为持久性的衡量标准。综上所述,这些数据进一步证明鹿鼠体内的 LNB 和 HMB 具有独特的神经生物学基础。因此,由鹿小鼠表达的自然发生的强迫性行为可能有助于提供一个平台来测试针对强迫症和相关疾病的不同症状维度的独特治疗目标。

更新日期:2020-07-13
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