Abstract:
Meta-chlorophenylpiperazine (mCPP) was one of the first compounds used in clinical and preclinical studies that demonstrated the role of serotonin in Obsessive-Compulsive Disorder (OCD). This systematic review aimed to (a) identify publications that report in rodents the effects of mCPP relevant to OCD, (b) explore the methodological characteristics of these studies, and (c) summarize the profile of mCPP effects. A comprehensive literature search was performed using PubMed, Scopus, and Web of Science. Search terms were a combination of obsessive-compulsive disorder or OCD and meta-chlorophenylpiperazine or mCPP. Twenty-nine articles were included in the review. The years of publication ranged from 1993 to 2021. Most studies used adult male Wistar or Sprague-Dawley rats. The most frequent dose of mCPP was 1.0 mg/kg administered acutely, intraperitoneally. In general, available preclinical evidence suggests increased defensive and compulsive behaviors associated with a decreased locomotor activity. But other results besides these and the absence of significant mCPP effects were also observed. Among the factors that may contribute to the variability of mCPP effects, differences in methods are highlighted, such as characteristics of the species/strains studied, mCPP doses and treatment regimens used. The heterogeneity of the OCD-like behaviors evaluated and the interaction of mCPP with different receptors may also be critical variables for discrepancies in the findings with mCPP. The information described in this review may contribute to a better understanding of how mCPP-induced behavioral changes in rodents have been used to study OCD, highlighting the main challenges for future investigations in this field.
摘要:
间氯苯基哌嗪(mCPP)是临床和临床前研究中最早使用的化合物之一,证明了5-羟色胺在强迫症(OCD)中的作用。本系统综述旨在(a)确定在啮齿动物中报告与强迫症相关的mCPP影响的出版物,(b)探讨这些研究的方法特点,(C)总结了mCPP效应的概况。使用PubMed进行了全面的文献检索,Scopus,和WebofScience。搜索词是强迫症或强迫症与间氯苯基哌嗪或mCPP的组合。审查中包括29篇文章。出版年份从1993年到2021年不等。大多数研究使用成年雄性Wistar或Sprague-Dawley大鼠。mCPP的最常见剂量为1.0mg/kg,腹膜内。总的来说,现有的临床前证据表明,与运动活动减少相关的防御和强迫行为增加。但也观察到除此之外的其他结果和不存在显著的mCPP效应。在可能导致mCPP效应变异性的因素中,方法上的差异被强调,例如所研究的物种/菌株的特征,使用的mCPP剂量和治疗方案。所评估的OCD样行为的异质性以及mCPP与不同受体的相互作用也可能是mCPP发现差异的关键变量。本综述中描述的信息可能有助于更好地理解mCPP诱导的啮齿动物行为变化如何用于研究强迫症,强调了这一领域未来调查的主要挑战。