Early life stress induces submissive behavior in adult rats

Frank, Dmitry; Zlotnik, Alexander; Kofman, Ora; Grinshpun, Julia; Severynovska, Olena; Brotfain, Evgeni; Kut, Ruslan; Natanel, Dmitry; Melamed, Israel; Boyko, Matthew

doi:10.1016/j.bbr.2019.112025

Cited by 14 publications

(11 citation statements)

References 71 publications

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“…Two days before testing, the rats were acclimated to the device with one 15-minute session every day. The apparatus consisted of two transparent Plexiglas boxes (30 cm × 20 cm × 20 cm) connected by a narrow passage (15 cm × 15 cm × 60 cm) [ 65 ]. A feeder containing sweetened milk was placed in the middle of the passage [ 47 , 65 ].…”

Section: Methodsmentioning

confidence: 99%

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Traumatic brain injury-induced submissive behavior in rats: link to depression and anxiety

et al. 2022

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Traumatic brain injury (TBI) affects millions of people worldwide, many of whom are affected with post-TBI mood disorders or behavioral changes, including aggression or social withdrawal. Diminished functionality can persist for decades after TBI and delay rehabilitation and resumption of employment. It has been established that there is a relationship between these mental disorders and brain injury. However, the etiology and causal relationships behind these conditions are poorly understood. Rodent models provide a helpful tool for researching mood disorders and social impairment due to their natural tendencies to form social hierarchies. Here, we present a rat model of mental complications after TBI using a suite of behavioral tests to examine the causal relationships between changes in social behavior, including aggressive, hierarchical, depressive, and anxious behavior. For this purpose, we used multivariate analysis to identify causal relationships between the above post-TBI psychiatric sequelae. We performed statistical analysis using principal component analysis, discriminant analysis, and correlation analysis, and built a model to predict dominant-submissive behavior based on the behavioral tests. This model displayed a predictive accuracy of 93.3% for determining dominant-submissive behavior in experimental groups. Machine learning algorithms determined that in rats, aggression is not a principal prognostic factor for dominant-submissive behavior. Alternatively, dominant-submissive behavior is determined solely by the rats’ depressive-anxious state and exploratory activity. We expect the causal approach used in this study will guide future studies into mood conditions and behavioral changes following TBI.

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Section: Methodsmentioning

confidence: 99%

“…The apparatus consisted of two transparent Plexiglas boxes (30 cm × 20 cm × 20 cm) connected by a narrow passage (15 cm × 15 cm × 60 cm) [ 65 ]. A feeder containing sweetened milk was placed in the middle of the passage [ 47 , 65 ]. Only one rat was able to fit in the feeder area at a time.…”

Section: Methodsmentioning

confidence: 99%

Traumatic brain injury-induced submissive behavior in rats: link to depression and anxiety

et al. 2022

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“…MS in early life induces hyperactivity of the HPA axis that is long-lasting, even in adulthood [ 67 , 68 ]. In fact, many studies of repeated MS during the first two weeks in rodents caused depression and anxiety-like behaviors in adulthood [ 69 , 70 , 71 , 72 , 73 ]. In these studies, the locomotor activity and rearing behaviors decreased, while the immobility during a forced swim test and the time spent in the closed arms of an elevated plus maze increased.…”

Section: Alterations In Behaviors Induced By Msmentioning

confidence: 99%

Effects of Early-Life Stress on the Brain and Behaviors: Implications of Early Maternal Separation in Rodents

Nishi

2020

IJMS

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Early-life stress during the prenatal and postnatal periods affects the formation of neural networks that influence brain function throughout life. Previous studies have indicated that maternal separation (MS), a typical rodent model equivalent to early-life stress and, more specifically, to child abuse and/or neglect in humans, can modulate the hypothalamic–pituitary–adrenal (HPA) axis, affecting subsequent neuronal function and emotional behavior. However, the neural basis of the long-lasting effects of early-life stress on brain function has not been clarified. In the present review, we describe the alterations in the HPA-axis activity—focusing on serum corticosterone (CORT)—and in the end products of the HPA axis as well as on the CORT receptor in rodents. We then introduce the brain regions activated during various patterns of MS, including repeated MS and single exposure to MS at various stages before weaning, via an investigation of c-Fos expression, which is a biological marker of neuronal activity. Furthermore, we discuss the alterations in behavior and gene expression in the brains of adult mice exposed to MS. Finally, we ask whether MS repeats itself and whether intergenerational transmission of child abuse and neglect is possible.

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“…To understand how ELS alters neurobiology in a way that promotes such aberrant behavior, many studies have used rodent models of maternal separation in which early postnatal pups are deprived of necessary maternal care by separating them from the dam for extended periods of time (for reviews see Nishi, Horii-Hayashi, & Sasagawa, 2014;Orso et al, 2019;Tractenberg et al, 2016). Rodent maternal separation during the early postnatal period has been shown to produce an array of adolescent and adulthood behavioral effects not limited to increased anxiety-like behavior (Caldji, Diorio, & Meaney, 2000;Daniels, Pietersen, Carstens, & Stein, 2004;Lee et al, 2007;Levine, 1967;Liu, Diorio, Day, Francis, & Meaney, 2000;Matthews, Hall, Wilkinson, & Robbins, 1996), hyper-responsiveness to stressors (Holmes et al, 2005;Meaney, 2001;Ogawa et al, 1994;Plotsky & Meaney, 1993), altered reward learning and cognition (Forster, Anderson, Scholl, Lukkes, & Watt, 2018;Liu et al, 2000;Matthews & Robbins, 2003;Portero-Tresserra et al, 2018;Pryce, Bettschen, Nanz-Bahr, & Feldon, 2003;Sasagawa et al, 2017), deviations in normal fear learning and memory (Callaghan, Graham, Li, & Richardson, 2013;Chocyk et al, 2014), and deficits in social behavior (Frank et al, 2019;Kompier, Keysers, Gazzola, Lucassen, & Krugers, 2019;Venerosi, Cirulli, Capone, & Alleva, 2003;Wang et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Chemogenetic manipulation of the bed nucleus of the stria terminalis counteracts social behavioral deficits induced by early life stress in C57BL/6J mice

Emmons

Sadok

Rovero

et al. 2020

J of Neuroscience Research

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Trauma during critical periods of development can induce long‐lasting adverse effects. To study neural aberrations resulting from early life stress (ELS), many studies utilize rodent maternal separation, whereby pups are intermittently deprived of maternal care necessary for proper development. This can produce adulthood behavioral deficits related to anxiety, reward, and social behavior. The bed nucleus of the stria terminalis (BNST) encodes aspects of anxiety‐like and social behaviors, and also undergoes developmental maturation during the early postnatal period, rendering it vulnerable to effects of ELS. Mice underwent maternal separation (separation 4 hr/day during postnatal day (PD)2–5 and 8 hr/day on PD6‐16) with early weaning on PD17, which induced behavioral deficits in adulthood performance on two‐part social interaction task designed to test social motivation (choice between a same‐sex novel conspecific or an empty cup) and social novelty preference (choice between the original‐novel conspecific vs. a new‐novel conspecific). We used chemogenetics to non‐selectively silence or activate neurons in the BNST to examine its role in social motivation and social novelty preference, in mice with or without the history of ELS. Manipulation of BNST produced differing social behavior effects in non‐stressed versus ELS mice; social motivation was decreased in non‐stressed mice following BNST activation, but unchanged following BNST silencing, while ELS mice showed no change in social behavior after BNST activation, but exhibited enhancement of social motivation—for which they were deficient prior—following BNST silencing. Findings emphasize the BNST as a potential therapeutic target for social anxiety disorders instigated by childhood trauma.

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Early life stress induces submissive behavior in adult rats

Cited by 14 publications

References 71 publications

Traumatic brain injury-induced submissive behavior in rats: link to depression and anxiety

Traumatic brain injury-induced submissive behavior in rats: link to depression and anxiety

Effects of Early-Life Stress on the Brain and Behaviors: Implications of Early Maternal Separation in Rodents

Chemogenetic manipulation of the bed nucleus of the stria terminalis counteracts social behavioral deficits induced by early life stress in C57BL/6J mice

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