Role of early environmental enrichment on the social dominance tube test at adulthood in the rat.

RATIONALE: Environmental enrichment (EE) could influence brain plasticity and behavior in rodents. Whether the early EE may predispose individuals to a particular social hierarchy in the social dominance tube test (SDTT) at adulthood is still unknown. OBJECTIVE: The present study directly investigated the influence of EE on competitive success in the SDTT among adult rats. METHODS: Male rats were maintained in EE from postnatal days 21 to 35. Social dominance behavior was determined by SDTT, competitive food foraging test, and mate preference test at adulthood. IBA-1 expression in the hypothalamus was examined using immunohistochemistry and western blot. RESULTS: EE rats were prone to become submissive during a social encounter with standard environment (SE) rats in the SDTT. No difference was found in food foraging in the competitive food foraging test between SE and EE rats. Male EE rats were more attractive than the SE to the female rats in the mate preference test. IBA-1 expression was found to be decreased in the hypothalamus of EE rats compared to SE group. Infusion of a microglia inhibitor reduced percentage of forward in SE rats in the SDTT. Infusion of DNA methyltransferase inhibitor prevented the development of subordinate status in EE rats and restored the expression of IBA-1 in the hypothalamus. CONCLUSIONS: The results suggest that early EE did not lead to reduced social hierarchy in the male rat. However, EE caused a reduction in the percentage of forward in the SDTT, which might be associated with reduced number of microglia in the hypothalamus.

Early-Life Social Isolation-Induced Depressive-Like Behavior in Rats Results in Microglial Activation and Neuronal Histone Methylation that Are Mitigated by Minocycline.

Early-life stress is a potent risk factor for development of psychiatric conditions such as depression. The underlying mechanisms remain poorly understood. Here, we used the early-life social isolation (ESI) model of early-life stress in rats to characterize development of depressive-like behavior, the role of microglia, levels of histone methylation, as well as expression of glutamate receptor subunits in the hippocampus. We found that depressive-like behavior was induced after ESI as determined by sucrose preference and forced swimming tests. Increased expression of microglial activation marker, Iba1, was observed in the hippocampus of the ESI group, while expression of the microglial CD200 receptor, which promotes microglial quiescence, significantly decreased. In addition, increased levels of proinflammatory cytokines, interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were observed in the hippocampus of the ESI group. Moreover, ESI increased levels of neuronal H3K9me2 (a repressive marker of transcription) and its associated "writer" enzymes, G9a and G9a-like protein, in the hippocampus. ESI also decreased expression of hippocampal NMDA receptor subunits, NR1, and AMPA receptor subunits, GluR1 and GluR2, which are involved in synaptic plasticity, but it did not affect expression of PSD95 and NR2B. Interestingly, treatment with minocycline to block microglial activation induced by ESI inhibited increases in hippocampal microglia and prevented ESI-induced depressive-like behavior as well as increases in IL-1ß, IL-6, and TNF-α. Notably, minocycline also triggered downregulation of H3K9me2 expression and restored expression of NR1, GluR1, and GluR2. These results suggest that ESI induces depressive-like behavior, which may be mediated by microglial signaling.