Enriched environment combined with fluoxetine ameliorates depression-like behaviors and hippocampal SYP expression in a rat CUS model

Liu, Cong; Gu, Jing; Han, Jin; Yan, Fu Lin; Li, Yan; Lv, Ting; Zhao, Li; Shao, Qiu Jing; Feng, Yan; Zhang, Xiang Y; Wang, Changhong

doi:10.1016/j.brainresbull.2017.09.009

Cited by 25 publications

(25 citation statements)

References 57 publications

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“…Thus, our results point to the direction that exposure to short daily environmental enrichment produces beneficial effects on anhedonia and coat deterioration analyzed during the pharmacological treatment with FLX. Our results with FLX plus ENR are similar to those findings in which adult male Sprague-Dawley rats were treated with FLX or its combination with environmental enrichment, 12 h a day, during three weeks of the pharmacological intervention [44].…”

Section: Behavioral Changes In Response To Chronic Mild Stress and Pharmacological Or Environmental Interventionssupporting

confidence: 87%

“…In our study, we found that FLX (10 mg/kg) reverses anhedonia in female Balb/C mice. Similarly, adult male Sprague-Dawley rats exposed to chronic unpredictable stress exhibited depression-like behavior (anhedonia) [44] that reverted after the pharmacological treatment with 10 mg/kg of FLX [44]. Additionally, other authors reported similar results caused by FLX (10 mg/kg) in Balb/C mice [45] and CD-1 mice [46].…”

Section: Behavioral Changes In Response To Chronic Mild Stress and Pharmacological Or Environmental Interventionsmentioning

confidence: 75%

“…Despite the benefits produced by short periods of environmental enrichment, the mechanisms explaining the contribution of short daily exposure to environmental enrichment to the benefits of FLX on behavior are challenging to explain because studies using short exposure to environmental enrichment are scarce. In this sense, FLX treatment in adult male Sprague-Dawley rats exposed to environmental enrichment during chronic unpredictable stress reverted anhedonia and alterations in the expression of proteins located in synapsis, suggesting the importance of synaptic plasticity to amplify the antidepressant effect of FLX [44]. Additionally, exposure to restricted environmental enrichment increased the expression of BDNF and its tropomyosin kinase B receptor in the hippocampus of rats, suggesting that restricted exposure to environmental enrichment boosted the benefits of fluoxetine [54].…”

Section: Behavioral Changes In Response To Chronic Mild Stress and Pharmacological Or Environmental Interventionsmentioning

confidence: 93%

“…However, the absence of a significant effect of a short daily environmental enrichment may also lead us to consider that other neuroplastic mechanisms are involved in the beneficial effects of this intervention combined with FLX. For example, FLX, environmental enrichment, or their combination increased synaptophysin expression and reversed anhedonia suggesting that these interventions may rebuild or repair the functioning of synaptic plasticity seen in unstressed rats [44]. Thus, the evidence suggests that additional mechanisms to regulate the neurogenic process may involve the beneficial effects of a short daily environmental enrichment exposure.…”

Section: Neurogenic Changes In Response To Chronic Mild Stress and Pharmacological Or Environmental Interventionsmentioning

confidence: 99%

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Short Daily Exposure to Environmental Enrichment, Fluoxetine, or Their Combination Reverses Deterioration of the Coat and Anhedonia Behaviors with Differential Effects on Hippocampal Neurogenesis in Chronically Stressed Mice

Ramírez-Rodríguez

Vega‐Rivera

Juan

et al. 2021

IJMS

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Depression is a neuropsychiatric disorder with a high impact on the worldwide population. To overcome depression, antidepressant drugs are the first line of treatment. However, pre-clinical studies have pointed out that antidepressants are not entirely efficacious and that the quality of the living environment after stress cessation may play a relevant role in increasing their efficacy. As it is unknown whether a short daily exposure to environmental enrichment during chronic stress and antidepressant treatment will be more effective than just the pharmacological treatment, this study analyzed the effects of fluoxetine, environmental enrichment, and their combination on depressive-associated behavior. Additionally, we investigated hippocampal neurogenesis in mice exposed to chronic mild stress. Our results indicate that fluoxetine reversed anhedonia. Besides, fluoxetine reversed the decrement of some events of the hippocampal neurogenic process caused by chronic mild stress. Conversely, short daily exposure to environmental enrichment changed the deterioration of the coat and anhedonia. Although, this environmental intervention did not produce significant changes in the neurogenic process affected by chronic mild stress, fluoxetine plus environmental enrichment showed similar effects to those caused by environmental enrichment to reverse depressive-like behaviors. Like fluoxetine, the combination reversed the declining number of Ki67, doublecortin, calretinin cells and mature newborn neurons. Finally, this study suggests that short daily exposure to environmental enrichment improves the effects of fluoxetine to reverse the deterioration of the coat and anhedonia in chronically stressed mice. In addition, the combination of fluoxetine with environmental enrichment produces more significant effects than those caused by fluoxetine alone on some events of the neurogenic process. Thus, environmental enrichment improves the benefits of pharmacological treatment by mechanisms that need to be clarified.

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Section: Behavioral Changes In Response To Chronic Mild Stress and Pharmacological Or Environmental Interventionssupporting

confidence: 87%

Section: Behavioral Changes In Response To Chronic Mild Stress and Pharmacological Or Environmental Interventionsmentioning

confidence: 75%

Section: Behavioral Changes In Response To Chronic Mild Stress and Pharmacological Or Environmental Interventionsmentioning

confidence: 93%

Section: Neurogenic Changes In Response To Chronic Mild Stress and Pharmacological Or Environmental Interventionsmentioning

confidence: 99%

See 2 more Smart Citations

Short Daily Exposure to Environmental Enrichment, Fluoxetine, or Their Combination Reverses Deterioration of the Coat and Anhedonia Behaviors with Differential Effects on Hippocampal Neurogenesis in Chronically Stressed Mice

Ramírez-Rodríguez

Vega‐Rivera

Juan

et al. 2021

IJMS

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“…As suggested previously, the combination therapy of TSD and other therapy, light therapy, for instance, have positive short-term and long-term effects even in patients who have been diagnosed with treatment-resistant depression (11). Meanwhile, antidepressants have been acknowledged and used as the standard treatment for major depressive disorders (MDDs); however, their efficacy tends to be variable and incomplete (12). As one of the most prescribed antidepressants, fluoxetine plays a vital role in MDD treatment and has been approved for clinical use, with effects on neurocognitive functions in adults with depression (13,14).…”

Section: Introductionmentioning

confidence: 99%

Rapid Eye Movement Sleep Deprivation Combined With Fluoxetine Protects Against Depression-Induced Damage and Apoptosis in Rat Hippocampi via A1 Adenosine Receptor

Wang

Pan

et al. 2021

Front. Psychiatry

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Background: Rapid eye movement sleep deprivation (REMSD) and fluoxetine affect depression, yet the detailed molecular mechanisms were not clear.Methods: Rat depression chronic unpredictable stress was constructed, and the body weight of rats was measured. The efficacy of REMSD and fluoxetine on the pleasure experience, exploration, and cognition of rats with depression was determined by the Sucrose preference test, the open field test, and Morris water task, respectively. The effects of REMSD and fluoxetine on depression-induced damage and apoptosis in rat hippocampi were detected using hematoxylin–eosin staining and terminal transferase-mediated biotin 2′-deoxyuridine, 5′-triphosphate nick end labeling. A1 adenosine receptor content was measured by immunohistochemistry. Relative expressions of the A1 adenosine receptor, proteins related to apoptosis (B Bcl-2-associated X protein; B-cell lymphoma 2), phosphoinositide 3-kinase, P38 mitogen-activated protein kinase, cFos, and adenosine deaminase RNA specific two were quantified by quantitative real-time polymerase chain reaction and Western blot as needed.Results: Depression decreased rat weight. REMSD combined with fluoxetine increased body weight, prompted rat behavior, alleviated depression-induced damage, attenuated apoptosis, and promoted A1 adenosine receptor level in rat hippocampi. Furthermore, the combined therapy upregulated expressions of A1 adenosine receptor, B-cell lymphoma 2, and phosphoinositide 3-kinase but downregulated those of B-cell lymphoma 2-associated X protein, P38 mitogen-activated protein kinase, cFos, and adenosine deaminase RNA specific 2 in the hippocampi of rats with depression.Conclusion:REMSD combined with fluoxetine protected rats against depression-induced damage and apoptosis in the hippocampus via the A1 adenosine receptor, providing a possible treatment strategy for depression.

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Environmental enrichment initiated in adolescence restores the reduced expression of synaptophysin and GFAP in the hippocampus of chronically stressed rats in a sex‐specific manner

Dandi,

Theotokis,

Petri

et al. 2023

Developmental Psychobiology

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This study aims at investigating whether environmental enrichment (EE) initiated in adolescence can alter chronic unpredictable stress (CUS)‐associated changes in astroglial and synaptic plasticity markers in male and female rats. To this end, we studied possible alterations in hippocampal glial fibrillary acidic protein (GFAP) and synaptophysin (SYN) in CUS rats previously housed in EE. Wistar rats on postnatal day (PND) 23 were housed for 10 weeks in standard housing (SH) or enriched conditions. On PND 66, animals were exposed to CUS for 4 weeks. SYN and GFAP expressions were evaluated in CA1 and CA3 subfields and dentate gyrus (DG). CUS reduced the expression of SYN in all hippocampal areas, whereas lower GFAP expression was evident only in CA1 and CA3. The reduced expression of SYN in DG and CA3 was evident to male SH/CUS rats, whereas the reduced GFAP expression in CA1 and CA3 was limited to SH/CUS females. EE housing increased the hippocampal expression of both markers and protected against CUS‐associated decreases. Our findings indicate that the decreases in the expression of SYN and GFAP following CUS are region and sex‐specific and underline the neuroprotective role of EE against these CUS‐associated changes.

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Enriched environment combined with fluoxetine ameliorates depression-like behaviors and hippocampal SYP expression in a rat CUS model

Cited by 25 publications

References 57 publications

Short Daily Exposure to Environmental Enrichment, Fluoxetine, or Their Combination Reverses Deterioration of the Coat and Anhedonia Behaviors with Differential Effects on Hippocampal Neurogenesis in Chronically Stressed Mice

Short Daily Exposure to Environmental Enrichment, Fluoxetine, or Their Combination Reverses Deterioration of the Coat and Anhedonia Behaviors with Differential Effects on Hippocampal Neurogenesis in Chronically Stressed Mice

Rapid Eye Movement Sleep Deprivation Combined With Fluoxetine Protects Against Depression-Induced Damage and Apoptosis in Rat Hippocampi via A1 Adenosine Receptor

Environmental enrichment initiated in adolescence restores the reduced expression of synaptophysin and GFAP in the hippocampus of chronically stressed rats in a sex‐specific manner

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