Intermittent environmental enrichment induces behavioral despair, while intermittent social isolation impairs spatial learning in rats

Environmental enrichment and social isolation constitute two well-studied experimental manipulations that result in several behavioral, neural, and molecular changes in rodents. Enrichment is linked to enhanced cognitive performance, and mitigation of different nervous system injuries and disorders. In contrast, social isolation or impoverished environment often induce negative effects on cognitive and affective systems. Both manipulations are typically examined with a short-term or chronic exposure, which cannot capture the actual human experiences. In this study, we explored the behavioral and neural alterations led by intermittent environmental enrichment or social isolation in adult Wistar rats. Animals were assigned to an enriched condition (EC), isolation/impoverished condition (IC), or standard condition (SC). The differential housing protocol involved transferring the animals to their respective cages for two days at the end of each five-day standard housing period for 8 weeks. Enriched animals exhibited behavioral despair in the forced swim test without differential overall locomotor activity. In the Morris water maze, impoverished animals displayed a slower learning rate compared to the SC and EC groups. In line with this, the IC group had fewer parvalbumin (PV) immunopositive (+) cells in the CA1 and dentate gyrus. No differences were observed in PV+ cell levels in the amygdala, while the IC group had more c-Fos+ cells in the same region following acute restraint stress. These findings implicate that intermittent isolation or enrichment are sufficient to trigger distinct behavioral changes at the cognitive and affective domains, and pinpoint PV as a biomarker for environmentally induced alterations in hippocampal memory performance.