Behavioral Profiling in Early Adolescence and Early Adulthood of Male Wistar Rats After Short and Prolonged Maternal Separation

Abstract

Early-life stress and its possible correlations to genes, environment, and later health outcomes can only be studied retrospectively in humans. Animal models enable the exploration of such connections with prospective, well-controlled study designs. However, with the recent awareness of replicability issues in preclinical research, the reproducibility of results from animal models has been highlighted. The present study aims to reproduce the behavioral effects of maternal separation (MS) previously observed in the multivariate concentric square field TM (MCSF) test. A second objective was to replicate the adolescent behavioral profiles previously described in the MCSF test. Male rats, subjected to short or prolonged MS or standard rearing, were subjected to behavioral testing in early adolescence and early adulthood. As seen in previous studies, the behavioral effects of MS in the MCSF were small at both tested time points. When tested in early adolescence, the animals exhibited a similar behavioral profile as previously seen, and the finding of adolescent behavioral types was also reproduced. The distribution of animals into the behavioral types was different than in the initial study, but in a manner consistent with developmental theories, as the current cohort was younger than the previous. Notably, the Shelter seeker behavioral type persisted through development, while the Explorer type did not. The lack of basal behavioral effect after MS is in line with the literature on this MS paradigm; the working hypothesis is that the prolonged MS gives rise to a phenotype predisposed to negative health outcomes but which is not apparent without additional provocation.

Aberrant cortical projections to amygdala GABAergic neurons contribute to developmental circuit dysfunction following early life stress

“… 8 Exposure to MS, using a protocol very similar to that in the present manuscript, associates with behavioral changes including higher anxiety-like behavior in early adolescence (P22-35) in male rats. 52 , 53 , 54 , 55 , 56 …”

The Developmental Origins of Opioid Use Disorder and Its Comorbidities

“…In rodents and non-human primates, numerous studies have demonstrated that ELA results in behavioral phenotypes that suggest underlying dysfunction in reward-related brain regions (Molet et al, 2014 ; Andersen, 2015 , 2018 ; Wakeford et al, 2018 ; Bonapersona et al, 2019 ; Birnie et al, 2020 ). The particular behavioral outcomes of ELA in animal models can vary depending on the type, timing, and duration of the paradigm, the species and strain of animal, and the timing and type of behavioral assays (Schmidt M. V. et al, 2011 ; Molet et al, 2014 ; Andersen, 2015 ; Walker et al, 2017 ; Brenhouse and Bath, 2019 ; Demaestri et al, 2020 ; Lundberg et al, 2020 ), as well as sex (Kundakovic et al, 2013 ; Bath, 2020 ). While this poses a challenge for interpreting this vast literature, the variability also mirrors human experience; indeed, ELA in humans can take many different forms, such as poverty, trauma, physical or sexual abuse, and neglect, and these, in combination with other environmental and biological factors, likely contribute to individual differences in clinical outcomes (Shand et al, 2011 ; Daskalakis et al, 2013 ; Sheridan and McLaughlin, 2014 ; Strathearn et al, 2020 ), highlighting the sensitivity of the brain to different types of stressors during these developmental periods.…”

Early life stress influences basal ganglia dopamine receptors and novel object recognition of adolescent and adult rats

“…Several studies have shown that maternal separation changes the offspring’s neuroendocrine and behavioral stress response in an opposite direction to neonatal handling; maternally separated animals show increased anxiety-like behavior, depressive behavior and impaired cognitive functions ( Banqueri et al, 2017 , Daniels et al, 2004 , de Souza et al, 2022 , Huot et al, 2001 , Lee et al, 2007 , Tsotsokou et al, 2021 ). Other studies report no significant differences on the HPA axis, on adult anxiety-like behavior, and cognition between maternally separated and control animals ( Biagini et al, 1998 , Hulshof et al, 2011 , Lehmann et al, 1999 , Lehmann et al, 1998 , Lundberg et al, 2020 , Shalev and Kafkafi, 2002 ).…”