Selecting antidepressants according to a drug-by-environment interaction: A comparison of fluoxetine and minocycline effects in mice living either in enriched or stressful conditions

Poggini, S.; Bon, G. Matte; Golia, M; Albanese, N. Ciano; Viglione, Aurelia; Poleggi, Anna; Limatola, Cristina; Maggi, Laura; Branchi, Igor

doi:10.1016/j.bbr.2021.113256

Cited by 12 publications

(10 citation statements)

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“…More specifically, although fluoxetine increases the expression of pro ‐ inflammatory markers in male mice when administered in environmentally enriched conditions, it produces anti‐inflammatory effects in stressful environments (Alboni et al, 2016). In another study, fluoxetine had no effect on levels of inflammatory markers in adult female mice previously exposed to CUMS (Poggini et al, 2021). All aforementioned studies have shown that EE following CUMS produces anti‐inflammatory and protective effects against CUMS‐induced inflammatory responses in male rats.…”

Section: Resultsmentioning

confidence: 96%

“…Specifically, adult male and female animals that underwent CUMS and were then treated with fluoxetine while living in EE presented reduced depression‐like symptomatology. On the contrary, depression‐like behavior was worsened in animals treated with fluoxetine while being exposed to CUMS instead of EE (Alboni et al, 2017; Branchi et al, 2013; Liu et al, 2017; Poggini et al, 2021). Similarly, the antibiotic minocycline, a drug with neuroprotective and anti‐inflammatory properties, had the same antidepressant effects in previously stressed adult female mice either being administered under EE or CUMS conditions (Poggini et al, 2021).…”

Section: Resultsmentioning

confidence: 99%

“…On the contrary, depression‐like behavior was worsened in animals treated with fluoxetine while being exposed to CUMS instead of EE (Alboni et al, 2017; Branchi et al, 2013; Liu et al, 2017; Poggini et al, 2021). Similarly, the antibiotic minocycline, a drug with neuroprotective and anti‐inflammatory properties, had the same antidepressant effects in previously stressed adult female mice either being administered under EE or CUMS conditions (Poggini et al, 2021). Even a short‐duration exposure to EE enhanced fluoxetine action against depressive‐like phenotype caused by previous CUMS exposure in adult female mice (Ramírez‐Rodríguez et al, 2021).…”

Section: Resultsmentioning

confidence: 99%

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Τhe neuroprotective role of environmental enrichment against behavioral, morphological, neuroendocrine and molecular changes following chronic unpredictable mild stress: A systematic review

Dandi

Spandou

Dalla

et al. 2023

Eur J of Neuroscience

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Environmental factors interact with biological and genetic factors influencing the development and well‐being of an organism. The interest in better understanding the role of environment on behavior and physiology led to the development of animal models of environmental manipulations. Environmental enrichment (EE), an environmental condition that allows cognitive and sensory stimulation as well as social interaction, improves cognitive function, reduces anxiety and depressive‐like behavior and promotes neuroplasticity. In addition, it exerts protection against neurodegenerative disorders, cognitive aging and deficits aggravated by stressful experiences. Given the beneficial effects of EE on the brain and behavior, preclinical studies have focused on its protective role as an alternative, non‐invasive manipulation, to help an organism to cope better with stress. A valid, reliable and effective animal model of chronic stress that enhances anxiety and depression‐like behavior is the chronic unpredictable mild stress (CUMS). The variety of stressors and the unpredictability in the time and sequence of exposure to prevent habituation, render CUMS an ethologically relevant model. CUMS has been associated with dysregulation of the hypothalamic–pituitary–adrenal axis, elevation in the basal levels of stress hormones, reduction in brain volume, dendritic atrophy and alterations in markers of synaptic plasticity. Although numerous studies have underlined the compensatory role of EE against the negative effects of various chronic stress regimens (e.g. restraint and social isolation), research concerning the interaction between EE and CUMS is sparse. The purpose of the current systematic review is to present up‐to‐date research findings regarding the protective role of EE against the negative effects of CUMS.

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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Τhe neuroprotective role of environmental enrichment against behavioral, morphological, neuroendocrine and molecular changes following chronic unpredictable mild stress: A systematic review

Dandi

Spandou

Dalla

et al. 2023

Eur J of Neuroscience

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“…The undirected susceptibility to change model posits that SSRI treatment does not affect mood per se but, by increasing neural plasticity, increases the likelihood of a change in mood that is driven by the quality of the living conditions and defined by time [ 63 ]. Recent studies have demonstrated such a hypothesis both at preclinical [ 72 , 74 , 75 ] and clinical [ 67 , 68 , 76 , 77 ] levels. The dynamic nature of SSRI outcome has been described also for endpoints different from depression, such as vulnerability to obesity [ 78 ], and growing evidence suggests the same conceptual approach applies to interpret the action of other classes of drugs regulating plasticity, such as psychedelics [ 79 , 80 ].…”

Section: Discussionmentioning

confidence: 99%

Time moderates the interplay between 5-HTTLPR and stress on depression risk: gene x environment interaction as a dynamic process

et al. 2022

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The serotonin-transporter-linked promoter region (5-HTTLPR) has been widely investigated as contributing to depression vulnerability. Nevertheless, empirical research provides wide contrasting findings regarding its involvement in the etiopathogenesis of the disorder. Our hypothesis was that such discrepancy can be explained considering time as moderating factor. We explored this hypothesis, exploiting a meta analytic approach. We searched PubMed, PsychoINFO, Scopus and EMBASE databases and 1096 studies were identified and screened, resulting in 22 studies to be included in the meta-analyses. The effect of the 5-HTTLPR x stress interaction on depression risk was found to be moderated by the following temporal factors: the duration of stress (i.e. chronic vs. acute) and the time interval between end of stress and assessment of depression (i.e. within 1 year vs. more than 1 year). When stratifying for the duration of stress, the effect of the 5-HTTLPR x stress interaction emerged only in the case of chronic stress, with a significant subgroup difference (p = 0.004). The stratification according to time interval revealed a significant interaction only for intervals within 1 year, though no difference between subgroups was found. The critical role of time interval clearly emerged when considering only chronic stress: a significant effect of the 5-HTTLPR and stress interaction was confirmed exclusively within 1 year and a significant subgroup difference was found (p = 0.01). These results show that the 5-HTTLPR x stress interaction is a dynamic process, producing different effects at different time points, and indirectly confirm that s-allele carriers are both at higher risk and more capable to recover from depression. Overall, these findings expand the current view of the interplay between 5-HTTLPR and stress adding the temporal dimension, that results in a three-way interaction: gene x environment x time.

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“…Recently, neuroimaging studies have corroborated the context dependence of SSRI effects in healthy subjects, confirming that these drugs enhance neuroplasticity 10 . Preclinical studies have also demonstrated that, in different contexts, SSRI effects differ also at the molecular and cellular levels [11][12][13] .…”

Section: Mainmentioning

confidence: 99%

Transition From Depression to Mental Health: Toward an Operationalization of Plasticity

Branchi

Colli

Chiarotti

et al. 2023

Preprint

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Plasticity is the ability to modify brain and behavior and allows the transition from psychopathology to mental wellbeing. High plasticity has been associated to high susceptibility to contextual factors, e.g., living conditions, which ultimately drive plasticity outcome. Here, we exploited network analysis to show that plasticity – i.e., the susceptibility to modify depression score – can be assessed by measuring the symptom network connectivity: the weaker the connectivity, the higher the plasticity, resulting in a greater modification in mood symptoms. We analyzed the STAR*D dataset and proved that connectivity strength at baseline is weaker in responder compared to non-responder patients. Moreover, connectivity strength at baseline was inversely correlated with improvement in depression score (Pearson's r=-0.87) and susceptibility to change mood according to context (Pearson's r=-0.77). This operationalization of plasticity provides a mathematical tool to investigate and predict resilience, vulnerability and recovery, and to develop novel approaches for the prevention and treatment of depression.

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Selecting antidepressants according to a drug-by-environment interaction: A comparison of fluoxetine and minocycline effects in mice living either in enriched or stressful conditions

Cited by 12 publications

References 84 publications

Τhe neuroprotective role of environmental enrichment against behavioral, morphological, neuroendocrine and molecular changes following chronic unpredictable mild stress: A systematic review

Τhe neuroprotective role of environmental enrichment against behavioral, morphological, neuroendocrine and molecular changes following chronic unpredictable mild stress: A systematic review

Time moderates the interplay between 5-HTTLPR and stress on depression risk: gene x environment interaction as a dynamic process

Transition From Depression to Mental Health: Toward an Operationalization of Plasticity

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