Agomelatine, venlafaxine, and running exercise effectively prevent anxiety- and depression-like behaviors and memory impairment in restraint stressed rats

Abstract

Several severe stressful situations, e.g., natural disaster, infectious disease out break, and mass casualty, are known to cause anxiety, depression and cognitive impairment, and preventive intervention for these stress complications is worth exploring. We have previously reported that the serotonin-norepinephrine-dopamine reuptake inhibitor, venlafaxine, as well as voluntary wheel running are effective in the treatment of anxiety- and depression-like behaviors in stressed rats. But whether they are able to prevent deleterious consequences of restraint stress in rats, such as anxiety/depression-like behaviors and memory impairment that occur afterward, was not known. Herein, male Wistar rats were pre-treated for 4 weeks with anti-anxiety/anti-depressive drugs, agomelatine and venlafaxine, or voluntary wheel running, followed by 4 weeks of restraint-induced stress. During the stress period, rats received neither drug nor exercise intervention. Our results showed that restraint stress induced mixed anxiety- and depression-like behaviors, and memory impairment as determined by elevated plus-maze, elevated T-maze, open field test (OFT), forced swimming test (FST), and Morris water maze (MWM). Both pharmacological pre-treatments and running successfully prevented the anxiety-like behavior, especially learned fear, in stressed rats. MWM test suggested that agomelatine, venlafaxine, and running could prevent stress-induced memory impairment, but only pharmacological treatments led to better novel object recognition behavior and positive outcome in FST. Moreover, western blot analysis demonstrated that venlafaxine and running exercise upregulated brain-derived neurotrophic factor (BDNF) expression in the hippocampus. In conclusion, agomelatine, venlafaxine as well as voluntary wheel running had beneficial effects, i.e., preventing the restraint stress-induced anxiety/depression-like behaviors and memory impairment.

Comparative analysis of restraint stress-induced depressive-like phenotypes in C57BL/6N mice derived from three different sources

“…Upon exposure to repeated RST, all mice exhibited the expected depressive-like behaviors with at least 14 days of exposure to RST, as reflected by prolonged immobility, decreased locomotion, and thigmotactic responses (the time spent in the periphery) in the TST, FST, and OFT, all of which are widely used for assessing anxiety- and depressive-like behaviors in research using rodents [ 18 – 20 ]. These results are consistent with previous studies [ 17 , 23 , 24 ] which demonstrated adaptive behavioral changes, suggesting that C57BL/6 N mice derived from different sources develop a similar degree of depressive-like behaviors upon exposure to repeated RST.…”

Role of physical activity in ameliorating neuropsychiatric symptoms in Alzheimer disease: A narrative review

“…Similar to selective serotonin reuptake inhibitors, physical activity can also lead to raise in tryptophan and is a precursor of serotonin, resulting in an increased serotonin in the brain. Thus, it can avoid disruption of serotoninergic signaling and may have antidepression‐like effect on NPs . Both norepinephrine and serotonin stimulation are 2 important factors in enhanced brain‐derived neurotrophic factor (BDNF) transcription following physical exercise .…”

“…Thus, it can avoid disruption of serotoninergic signaling and may have antidepression-like effect on NPs. 60,61 Both norepinephrine and serotonin stimulation are 2 important factors in enhanced brainderived neurotrophic factor (BDNF) transcription following physical exercise. 57 It is well known that BDNF is a fundamental mediator to regulate neuronal survival, synaptic plasticitya, and neurogenesis in the brain, in particular in the hippocampus, which is the cerebral area mainly involved on memory and behavior.…”

<p>Protective Effects of <em>Spirulina platensis</em>, Voluntary Exercise and Environmental Interventions Against Adolescent Stress-Induced Anxiety and Depressive-Like Symptoms, Oxidative Stress and Alterations of BDNF and 5HT-3 Receptors of the Prefrontal Cortex in Female Rats</p>

“…Studies have shown that exercise improves cognitive deficits 48 , 49 and enhances levels of BDNF in the brain 50 , 51 and reduces the risk of neuropsychiatric diseases. 52 , 53 BDNF plays an important role in mediating the effects of exercise on brain functions. 50 Environmental enrichment (EE) is another beneficial intervention for improving anxiety and depression-like behaviors.…”