Antidepressive Effects of Environmental Enrichment in Chronic Stress–Induced Depression in Rats

Abstract

Depression is caused by a variety of factors, especially stressful life events. Chronic stress-induced depression has detrimental effects on hippocampal integrity. Environmental enrichment (EE) is a beneficial intervention for improving anxiety, fear, and stress. We aimed to investigate the antidepressive effects of EE in a depressive rat model (DEP) that was subjected to chronic stress. The control group ( n = 10) was kept under normal conditions, while depressive rats ( n = 8 per group) were randomized into DEP, DEP + EE, and DEP + fluoxetine (Flx) groups. DEP + EE/Flx groups were exposed to standard housing and EE or Flx, respectively. The behavioral tests showed that hopelessness and anxiety were decreased in DEP + EE and DEP + Flx groups compared with the DEP group ( p < .05). Similarly, the expression of vascular endothelial growth factor and tryptophan hydroxylase was significantly higher in the DEP + EE and DEP + Flx ( p < .05) groups. The levels of brain-derived neurotrophic factor and tyrosine receptor kinase B were also significantly higher in the DEP + EE and DEP + Flx groups compared with the DEP group ( p < .05). Our findings can serve as a foundation for future investigations examining the effects of environmental improvement and physical exercise in patients with depression. This study suggests that EE may be useful for mitigating the detrimental effects of chronic stress in patients with depression.

Role of NDEL1 and VEGF/VEGFR-2 in Mouse Hippocampus After Status Epilepticus

“…VEGF alteration in CA1, CA3, and DG in the hippocampus, motor cortex, and cerebellum has been associated with multiple neuropsychiatric diseases, such as cerebral ischemia (Zhou et al., 2017; Song et al., 2019), brain injury (Xu et al., 2016), epilepsy (Choi, Lee, Chang, et al., 2016; Tawfik et al., 2018), and depression (Wang et al., 2014; Seong et al., 2018). Especially, in recent studies on epilepsy, a large body of evidence has emerged suggesting that VEGF not only regulates angiogenesis and vascular permeability but is also involved in neuronal protection in hippocampus.…”

Brain-Derived Neurotrophic Factor: A Key Molecule for Memory in the Healthy and the Pathological Brain

“…Seong et al (2018) suggested that EE is as effective as Fluoxetine when it occurs after exposure of the animals to a chronic stress protocol, but additional measures of the effectiveness of the stress protocol would be needed to establish the success of the treatment. Interestingly, BDNF levels were increased in the hippocampus of rats that receive either EE or Fluoxetine in comparison with the control group (stressed but without posterior treatment).…”

Differential impact of stress and environmental enrichment on corticolimbic circuits

“…Similar beneficial effects are also observed in the domains of mood and cognitive processing. Beneficial effects of EE on mood are manifested as decreased anhedonia in the sucrose preference test (SPT) [46][47][48] , increased active coping in the forced swim test (FST) [46][47][48][49][50] , and increased resilience to social defeat 51 . EE also improves learning and memory in passive avoidance tests 52 , spatial memory in the radial arm maze 53,54 and Morris water maze 24,39,[55][56][57][58][59][60] , and reversal learning in operant touchscreen tasks 61 .…”

“…Hippocampal brain derived neurotrophic factor (BDNF), in particular, is increased by EE under basal conditions 99,103,113,140,[163][164][165][166] . EE prevents stress-induced decreases in BDNF, which are believed to contribute to the maladaptive behavioral effects of stress 50,63,64,66,68,167,168 . The receptor for BDNF, tropomyosin receptor kinase B (TrkB), is also increased by EE and exercise 50,169 .…”