Stress-mediated hyperactivity and anhedonia resistant to diazepam and fluoxetine in Drosophila

Distresses may induce behavioral phenotypes constituting heuristic models for psychopharmacology studies. In several species, including Drosophila, antidepressants counteract stress-induced phenotypes allowing the use of these models to test new psychoactive drugs. Here, we developed a novel and time-efficient protocol to provoke stress-induced phenotypes in Drosophila for the study of psychopharmacological agents. In the first experiment, flies (n = 12/groups) were exposed to a random-sequence of different types of stresses during nearly 24 h (including social isolation, fasting, heat, and electric shock), a protocol named short-term variable stress (SVS). Second, flies were exposed to a single stressful stimulus (social isolation, fasting, heat shock or electric shock, n = 12/groups). Next, flies submitted to SVS protocol were treated with vehicle, diazepam or fluoxetine (n = 12/groups). At the end of the stress protocols, behavioral phenotypes were evaluated in the open field (OF) and sucrose preference tests. In comparison to the unstressed group, flies exposed to SVS exhibited hyperactivity, as well as shorter times exploring the boundaries of the OF. In contrast to fasting stress, SVS reduced sucrose preference in flies. By analyzing the effects of individual stimuli on fly behavior, fasting and electric shock appear to be the predominant influences on the SVS-induced behaviors. Although fluoxetine or diazepam reduced the initial locomotor activity of flies, no treatment prevented the sequelae of SVS. Altogether, this study provides a time-efficient model system for the study of stress-mediated hyperactivity and anhedonia-like state resistant to fluoxetine and diazepam. The applications of SVS in Drosophila to preclinical psychopharmacology require further studies.LAY SUMMARY Exposition to unpredictable stress plays a significant role in psychiatric disorder’s onset. Behavioral traits of these disorders can be partially modeled in rodents aimed at developing psychopharmacological therapies. However, studies in rodents were questioned by ethical issues. Focused on 3Rs principles, we developed a preclinical model for stress and psychopharmacology research in Drosophila. Variable stress induced behavioral alterations, including hyperlocomotion and reduced preference for sucrose in flies. However, behavioral alterations were resistant to fluoxetine and diazepam.Fil: Ramos Hryb, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Ramirez, Mauro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Lino de Oliveira, Cilene. Universidade Federal de Santa Catarina; BrasilFil: Pagani, Mario Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

Justify your alpha

Benjamin et al. proposed changing the conventional “statistical significance” threshold (i.e.,the alpha level) from p ≤ .05 to p ≤ .005 for all novel claims with relatively low prior odds. They provided two arguments for why lowering the significance threshold would “immediately improve the reproducibility of scientific research.” First, a p-value near .05provides weak evidence for the alternative hypothesis. Second, under certain assumptions, an alpha of .05 leads to high false positive report probabilities (FPRP2 ; the probability that a significant finding is a false positive

Justify your alpha

In response to recommendations to redefine statistical significance to p ≤ .005, we propose that researchers should transparently report and justify all choices they make when designing a study, including the alpha level

Disciplina "Introdução à Revisão Sistemática e Meta-Análise"

Material usado nas seguintes disciplinas: 1-"Introdução à Revisão Sistemática e Meta-Análise em Farmacologia Básica" (FMC510046-41000242DO/ME) do PPG em Farmacologia da UFSC; 2-Introdução a Revisão Sistemática e Meta-análise (EEL510425-41000056DO) - do PPPG em engenharia Elétrica da UFSC

Systematic heterogenisation to improve reproducibility in animal studies.

A recent study published in PLOS Biology investigated whether the systematic use of multiple experimenters boosts the reproducibility of behavioural assays in mice. These findings open up prospects for solutions to reproducibility issues in animal research

Protocol for systematic review and meta-analysis of the evidence linking hippocampal neurogenesis to the effects of antidepressants on mood and behaviour

Objective Studies in rodents associated the deficits of adult hippocampal neurogenesis with behavioural anomalies which may be reversed by antidepressant treatments. A previous systematic review (SR) and meta-analysis (MA) indicated a hierarchy within the proneurogenic effects of different antidepressants in naive rodents. The present review aims to evaluate a more comprehensive sample of studies investigating the links between the effects of different antidepressants and adult hippocampal neurogenesis.Search strategy, screening annotation, data management Protocols were planned following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Searches in Embase, Medline, Scopus and Web of Science followed by screening with inclusion/exclusion criteria will provide relevant publications. First SR will summarise the effects of antidepressants on adult hippocampal neurogenesis on different laboratory rodents. Second SR will summarise the correlations between neurogenic and behavioural effects of antidepressants while the third will focus on cause–effect relationships between them. If feasible, data will be analysed by pairwise or network random-effect or multivariate MA to determine the direction, magnitude, significance and heterogeneity (I2) of the estimated effect sizes on global or subgroup levels. Funnel plotting, Egger regression, ‘trim and fill’ will be used to estimate the risk of publication bias. Quality assessment of the included publications will be performed by applying adapted CAMARADES, Syrcles’ risk of bias or CINeMA tools.Reporting Find a preliminary version of this protocol at the Open Science Framework (https://osf.io/gmsvd/). Data extraction has already started. Results shall be published in a peer-reviewed journal. Due to the continuous production in the field, the implementation of a ‘living SR’ is intended

Early life stress and implications for the response of antidepressant treatment.

The hypothesis of this project is that the perinatal stress generates long-term behavioral modifications that are expressed in adult life as resistance to treatment with monoaminergic antidepressant drugs

Revisão Sistemática e Meta-análise para Farmacologistas

This project aims to propose a tool to assist pharmacologists and researchers from related fields in conducting Living Systematic Reviews