Environmental enrichment attenuates maternal separation-induced excessive hoarding behavior in adult female mice

Abstract

BackgroundPrevious studies have demonstrated that early life stress (ELS) impacts hoarding behavior in adult humans. This study aimed to assess the potential mitigation by environmental enrichment on hoarding behavior in rodents caused by maternal separation, thereby providing insights into therapeutic strategies for hoarding disorder. MethodsNewborn mice were randomly divided into four groups. The control group was allowed to grow naturally. The maternal separation group underwent two weeks of maternal separation. The short-term environmental enrichment group received two weeks of environmental enrichment intervention after the two weeks of maternal separation. The long-term environmental enrichment group received five weeks of environmental enrichment intervention after the two weeks of maternal separation. Hoarding behavior was assessed during adolescence and adulthood. Hippocampal tissue from adult female mice was analyzed using LC-MS/MS-based metabolomics. Spearman correlation analysis was then performed to assess the relationship between differentially expressed metabolites and hoarding behavior. ResultsEnvironmental enrichment attenuates maternal separation-induced excessive hoarding behavior in adult female mice. The untargeted metabolomics of the hippocampal region in female mice showed that long-term environmental enrichment reversed multiple differential metabolites, including Substance P, which were mainly concentrated in metabolic pathways such as cancer choline metabolism, glycolipid metabolism, and linoleic acid metabolism. ConclusionsOur findings indicate that ELS and long-term environmental enrichment have sex-dependent effects on adult hoarding behavior, potentially related to altered hippocampal metabolism. This study highlights the importance of environmental enrichment in mitigating the long-term effects of early maternal separation on hoarding behavior.