title: An overview of maternal separation effects on behavioural outcomes in mice: Evidence from a four-stage methodological systematic review.
abstract: Early life stress (ELS) developmental effects have been widely studied by preclinical researchers. Despite the growing body of evidence from ELS models, such as the maternal separation paradigm, the reported results have marked inconsistencies. The maternal separation model has several methodological pitfalls that could influence the reliability of its results. Here, we critically review 94 mice studies that addressed the effects of maternal separation on behavioural outcomes. We also discuss methodological issues related to the heterogeneity of separation protocols and the quality of reporting methods. Our findings indicate a lack of consistency in maternal separation effects: major studies of behavioural and biological phenotypes failed to find significant deleterious effects. Furthermore, we identified several specific variations in separation methodological procedures. These methodological variations could contribute to the inconsistency of maternal separation effects by producing different degrees of stress exposure in maternal separation-reared pups. These methodological problems, together with insufficient reporting, might lead to inaccurate and unreliable effect estimates in maternal separation studies.
authors.affiliation: Developmental Cognitive Neuroscience Lab (DCNL), Post-Graduate Program in Psychology, Pontifical Catholic University of Rio Grande do Sul (PUCRS), 6681 Ipiranga Avenue, Building 11, Room 928 Porto Alegre, RS, Brazil.
authors.forename: Saulo G
authors.initials: SG
authors.lastname: Tractenberg
authors.affiliation: Developmental Cognitive Neuroscience Lab (DCNL), Post-Graduate Program in Psychology, Pontifical Catholic University of Rio Grande do Sul (PUCRS), 6681 Ipiranga Avenue, Building 11, Room 928 Porto Alegre, RS, Brazil.
authors.forename: Mateus L
authors.initials: ML
authors.lastname: Levandowski
authors.affiliation: Developmental Cognitive Neuroscience Lab (DCNL), Post-Graduate Program in Psychology, Pontifical Catholic University of Rio Grande do Sul (PUCRS), 6681 Ipiranga Avenue, Building 11, Room 928 Porto Alegre, RS, Brazil; Post-Graduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil.
authors.forename: Lucas Araújo
authors.initials: LA
authors.lastname: de Azeredo
authors.affiliation: Developmental Cognitive Neuroscience Lab (DCNL), Post-Graduate Program in Psychology, Pontifical Catholic University of Rio Grande do Sul (PUCRS), 6681 Ipiranga Avenue, Building 11, Room 928 Porto Alegre, RS, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Orso
authors.affiliation: Developmental Cognitive Neuroscience Lab (DCNL), Post-Graduate Program in Psychology, Pontifical Catholic University of Rio Grande do Sul (PUCRS), 6681 Ipiranga Avenue, Building 11, Room 928 Porto Alegre, RS, Brazil.
authors.forename: Laura G
authors.initials: LG
authors.lastname: Roithmann
authors.affiliation: Developmental Cognitive Neuroscience Lab (DCNL), Post-Graduate Program in Psychology, Pontifical Catholic University of Rio Grande do Sul (PUCRS), 6681 Ipiranga Avenue, Building 11, Room 928 Porto Alegre, RS, Brazil.
authors.forename: Emerson S
authors.initials: ES
authors.lastname: Hoffmann
authors.affiliation: Department of Psychology, Northeastern University, 125 Nightingale Hall, 360 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Brenhouse
authors.affiliation: Developmental Cognitive Neuroscience Lab (DCNL), Post-Graduate Program in Psychology, Pontifical Catholic University of Rio Grande do Sul (PUCRS), 6681 Ipiranga Avenue, Building 11, Room 928 Porto Alegre, RS, Brazil; Post-Graduate Program in Pediatrics and Children Health⿿s, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil. Electronic address: rodrigo.grassi@pucrs.br.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Grassi-Oliveira
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D008426:Maternal Deprivation; D051379:Mice; D015203:Reproducibility of Results; D013315:Stress, Psychological
keywords: Early life stress; Early postnatal manipulation; Maternal deprivation; Maternal separation; Methodological review; Mice; Rodent