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.

Mónica Flores-Ramos,Erika Montserrat Estrada-Camarena,David Meneses-San Juan,Nelly Maritza Vega-Rivera,Gerardo Bernabé Ramírez-Rodríguez,Leonardo Ortiz-López

doi:10.3390/ijms222010976

Mónica Flores-Ramos, Erika Montserrat Estrada-Camarena + Show 4 more

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https://doi.org/10.3390/ijms222010976

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Abstract

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.

Highlights

Introduction conditions of the Creative CommonsDepression is characterized by neurochemical, neuroplastic, and behavioral alterations [1,2]
The relevance of these hippocampal subregions derives from studies that demonstrated the specific participation of the dorsal part in behaviors related to spatial navigation [13], whereas the ventral part of the hippocampus is associated with behaviors related to the mood [14,15]
Based on the above-mentioned evidence, we considered that the inclusion of a short daily exposure to environmental enrichment together with the pharmacological treatment during chronic mild stress could be relevant to increase the efficacy of antidepressant drugs

Summary

Introduction

Introduction conditions of the Creative CommonsDepression is characterized by neurochemical, neuroplastic, and behavioral alterations [1,2]. The neurochemical and behavioral improvement, antidepressant drugs favor plastic changes in the brain, including but not limited to the generation of new neurons in the dentate gyrus of the hippocampus [6,7,8]. In this regard, several antidepressant drugs such as fluoxetine and citalopram, both acting as selective serotonin reuptake inhibitors (SSRIs), have shown positive effects at the level of the generation of new neurons in the dentate gyrus of the hippocampus [9,10]. Hippocampal new neurons play a role in learning and memory processes and buffering stress exposure [11] In this sense, it has been shown that the increasing number of new neurons concurs with better behavior in animal models of depression [11]. The relevance of these hippocampal subregions derives from studies that demonstrated the specific participation of the dorsal part in behaviors related to spatial navigation [13], whereas the ventral part of the hippocampus is associated with behaviors related to the mood [14,15]

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