Meta-Chlorophenylpiperazine-Induced Behavioral Changes in Obsessive-Compulsive Disorder Research: A Systematic Review of Rodent Studies

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.

Keywords: Anxiety; Meta-chlorophenylpiperazine; Obsessive-Compulsive Disorder; Repetitive behavior; Rodents; Serotonin.