The differential effects of brief environmental enrichment following social isolation in rats

Abstract

Environmental enrichment (EE) in rodents is associated with a wide range of physiological, affective, and cognitive benefits. A seemingly opposite housing condition, social isolation (SI), is used as a rodent model of stress, negatively affecting several neurobiological mechanisms and hampering cognitive performance. Experimental designs that involve switching between these housing conditions produced mixed results. We evaluated different behavioral and cognitive effects of brief EE following long-term, SI-induced stress. We revealed the influence of enrichment after 30 days of isolation on behavioral despair, anxiety-like behavior, and spatial working memory in adult male Wistar rats and found a substantial anxiolytic effect in the experimental (SI to EE) group. Interestingly, rats exposed to EE also showed increased behavioral despair compared with the control (continuous SI) group. There was no difference in spatial working memory performance at the end of a 5-day water Y-maze (WYM) test. However, the SI to EE animals displayed better memory performance in the first 2 days of the WYM, indicating faster learning. In line with this difference, we recorded significantly more c-Fos-immunopositive (c-Fos+) cells in the retrosplenial and perirhinal cortices of the SI to EE animals. The lateral and basolateral nuclei of the amygdala showed no such difference. These results suggest that brief enrichment following isolation stress leads to differential results in affective and cognitive systems.

Environmental enrichment improves social isolation-induced memory impairment: The possible role of ITSN1-Reelin-AMPA receptor signaling pathway

“…laboratory animals demonstrated that EE resilience the SI induced impairment in working memory and reference memory [43,50,51], and spatial memory [29,43]. Specifically, EE resilience SI induced anxiety-like behaviour [52] and improve working memory in field-caught rodents [32,53].…”

“…On day 2, (i) Direct Wild (DW) group animals (n = 10) were subjected to hole-board test (HBT). Remaining animals (n = 35, 1/cage) were individually housed for social isolation (SI) in small standard laboratory cage (29.5×22×13cm) for ten days [43]. After the period of SI, animals were randomly divided into three groups: (ii) Short-Term at Standard Condition (STSC; n=10), housed at standard laboratory cage (43×27×15cm; 2-3/cage with Kleenex tissue paper as bedding) for seven days and then subjected to HBT; (iii) Long-Term at Standard Conditions (LTSC, n=10, 43×27×15cm; 2-3/cage with Kleenex tissue paper as bedding), which remained in the laboratory cage for another thirty days, then subjected to HBT.…”

Rodent tests of depression and anxiety: Construct validity and translational relevance

“…Rapid-acting antidepressants, such as ketamine (Akan et al, 2023 ; Ecevitoglu et al, 2019 ; Kingir et al, 2023 ), replicated the antidepressant-like effect. Nonpharmacological antidepressant manipulations, such as environmental enrichment (Guven et al, 2022 ), also may produce therapeutic effects, providing further support for considering FST as a general test of antidepressant efficacy. Acute (Ünal et al, 2022 ) or chronic stress models (Kingir et al, 2023 ), in contrast, worsen behavioral despair in the FST by further increasing immobility compared with control groups.…”

“…However, it does not explain how nonpharmacological antidepressant manipulations, such as environmental enrichment, prevents behavioral despair. Environmental enrichment has been shown to facilitate learning (Falkenberg et al, 1992 ; Guven et al, 2022 ; Schrijver et al, 2002 ); however, it often leads to a decrease in immobility in the FST. By restricting its argumentation to antidepressant drug use in the FST, the “coping strategy” interpretation found good support in the literature (Molendijk & de Kloet, 2019 ).…”