Modified limited bedding and nesting is a model of early-life stress that affects reproductive physiology and behavior in female and male Long-Evans rats

Davis, Lourdes K.; Bolton, Jessica L.; Hanson, Hannah; Guarraci, Fay A.

doi:10.1016/j.physbeh.2020.113037

Cited by 33 publications

(19 citation statements)

References 45 publications

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“…Together these findings corroborate with a recent study, which showed that LB and MS combined resulted in a robust increase in anxiety-like behavior, but LB alone was not sufficient to generate an anxiogenic phenotype (Johnson et al, 2018). Furthermore, several studies have also previously shown that animals reared in LB conditions did not present an increase in anxiety-like behavior during adulthood (Brunson et al, 2005;Rice et al, 2008;Goodwill et al, 2019;Davis et al, 2020;Wang et al, 2012). Those results are not restricted to LB protocol, since they are supported by a range of studies suggesting inconclusive effects of MS.…”

Section: Discussionsupporting

confidence: 90%

“…On the other hand, in a recent review from our laboratory (Orso et al, 2019), we found that MS alone induces an increase in the levels of licking/grooming post-reunion. This counterbalance behavior (increase in maternal care) could attenuate the deprivation characteristics of the MS model, and possibly minimize the effects of the separation period (Davis et al, 2020;Wang et al, 2020). Furthermore, during MS, pups are also exposed to an unknown environment, which is full of novel cues that can also have a direct impact on neurodevelopment.…”

Section: Discussionmentioning

confidence: 99%

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Maternal Separation Combined With Limited Bedding Increases Anxiety-Like Behavior and Alters Hypothalamic-Pituitary-Adrenal Axis Function of Male BALB/cJ Mice

Orso

Creutzberg

Kestering-Ferreira

et al. 2020

Front. Behav. Neurosci.

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Early life stress (ELS) is considered a risk factor for the development of psychiatric conditions, including depression and anxiety disorder. Individuals that live in adverse environments are usually exposed to multiple stressors simultaneously, such as maternal neglect, maltreatment, and limited resources. Nevertheless, most pre-clinical ELS models are designed to explore the impact of these events separately. For this reason, this study aims to investigate the effects of a combined model of ELS on anxiety-like behavior and hypothalamic-pituitary-adrenal (HPA) axis related targets. From PND 2 to PND 15 BALB/cJ mice were exposed simultaneously to maternal separation (MS; 3 h per day) and limited bedding (LB; ELS group) or left undisturbed (CT group). Maternal behavior was recorded in intercalated days, from PND 1 to PND 9. Male offspring were tested for anxiety-like behavior from PND 53 to PND 55 in the open field test (OF), elevated plus-maze (EPM), and light/dark test (LD). After behavioral testing, animals were euthanized, and glucocorticoid receptor ( Nr3c1) , corticotrophin-releasing hormone ( Crh ), and its receptor type 1 ( Crhr1 ) gene expression in the hypothalamus were measured. Moreover, plasma corticosterone levels were analyzed. We observed that ELS dams presented altered quality of maternal care, characterized by a decrease in arched-back nursing, and an increase in passive nursing. Stressed dams also showed an increase in the number of exits from the nest when compared to CT dams. Furthermore, ELS animals showed increased anxiety-like behavior in the OF, EPM, and LD. Regarding gene expression, we identified an increase in hypothalamus Crh levels of ELS group when compared to CT animals, while no differences in Nr3c1 and Crhr1 expression were observed. Finally, stressed animals showed decreased levels of plasma corticosterone when compared to the CT group. In conclusion, we observed an alteration in maternal behavior in ELS dams. Later in life, animals exposed to the combined model of ELS showed increased levels of anxiety-like behavior. Moreover, the central and peripheral HPA measures observed could indicate a dysregulation in HPA function provoked by ELS exposure.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Maternal Separation Combined With Limited Bedding Increases Anxiety-Like Behavior and Alters Hypothalamic-Pituitary-Adrenal Axis Function of Male BALB/cJ Mice

Orso

Creutzberg

Kestering-Ferreira

et al. 2020

Front. Behav. Neurosci.

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“…However, another study reported opposite findings in which female Sprague-Dawley rats exposed to LBN show increased motivation for food reward in a one-h free access task ( 106 ). To our knowledge, only one study has assessed the effect of ELS on motivation for access to a social reward ( 110 ). In this study, LBN increased sexual motivation in both male and female Long-Evans rats ( 110 ).…”

Section: Impact Of Early Life Stress On Motivated Behavior and Reward Circuit Activity From Non-human Animal Modelsmentioning

confidence: 99%

“…To our knowledge, only one study has assessed the effect of ELS on motivation for access to a social reward ( 110 ). In this study, LBN increased sexual motivation in both male and female Long-Evans rats ( 110 ). Whether ELS also increases other forms of social motivation is not yet known.…”

Section: Impact Of Early Life Stress On Motivated Behavior and Reward Circuit Activity From Non-human Animal Modelsmentioning

confidence: 99%

Impact of Early Life Stress on Reward Circuit Function and Regulation

et al. 2021

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Early life stress – including experience of child maltreatment, neglect, separation from or loss of a parent, and other forms of adversity – increases lifetime risk of mood, anxiety, and substance use disorders. A major component of this risk may be early life stress-induced alterations in motivation and reward processing, mediated by changes in the nucleus accumbens (NAc) and ventral tegmental area (VTA). Here, we review evidence of the impact of early life stress on reward circuit structure and function from human and animal models, with a focus on the NAc. We then connect these results to emerging theoretical models about the indirect and direct impacts of early life stress on reward circuit development. Through this review and synthesis, we aim to highlight open research questions and suggest avenues of future study in service of basic science, as well as applied insights. Understanding how early life stress alters reward circuit development, function, and motivated behaviors is a critical first step toward developing the ability to predict, prevent, and treat stress-related psychopathology spanning mood, anxiety, and substance use disorders.

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“…It remains possible that the MS model of ELS may impact the oxytocin system to a greater extent in males than in females, while other models of ELS (e.g., LBN model), may differentially affect oxytocin system development. For example, the LBN procedure elicited earlier onset of puberty in female rats, while delaying puberty in male rats [ 73 ], and oxytocin receptor and oxytocin expression are increased in females, but decreased in males exposed to limited bedding [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

Oxytocin as an adolescent treatment for methamphetamine addiction after early life stress in male and female rats

Baracz

Robinson

Wright

et al. 2022

Neuropsychopharmacol.

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Early life stress (ELS) is associated with perturbed neural development and augmented vulnerability to mental health disorders, including addiction. How ELS changes the brain to increase addiction risk is poorly understood, and there are no therapies which target this ELS-induced vulnerability. ELS disrupts the oxytocin system, which can modulate addiction susceptibility, suggesting that targeting the oxytocin system may be therapeutic in this ELS-addiction comorbidity. Therefore, we determined whether adolescent oxytocin treatment after ELS could: (1) reduce vulnerability to anxiety, social deficits, and methamphetamine-taking and reinstatement; and (2) restore hypothalamic oxytocin and corticotropin-releasing factor expressing neurons and peripheral oxytocin and corticosterone levels. Long Evans pups underwent maternal separation (MS) for either 15 min or 360 min on postnatal days (PND) 1–21. During adolescence (PNDs 28–42), rats received a daily injection of either oxytocin or saline. In Experiment 1, adult rats were assessed using the elevated plus-maze, social interaction procedure, and methamphetamine self-administration procedure, including extinction, and cue-, methamphetamine- and yohimbine-induced reinstatement. In Experiment 2, plasma for enzyme immunoassays and brain tissue for immunofluorescence were collected from adult rats after acute stress exposure. Adolescent oxytocin treatment ameliorated ELS-induced anxiety and reduced methamphetamine- and yohimbine-induced reinstatement in both sexes, and suppressed methamphetamine intake and facilitated extinction in males only. Additionally, adolescent oxytocin treatment after ELS restored oxytocin-immunoreactive cells and stress-induced oxytocin levels in males, and attenuated stress-induced corticosterone levels in both sexes. Adolescent oxytocin treatment reverses some of the ELS effects on later-life psychopathology and vulnerability to addiction.

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Modified limited bedding and nesting is a model of early-life stress that affects reproductive physiology and behavior in female and male Long-Evans rats

Cited by 33 publications

References 45 publications

Maternal Separation Combined With Limited Bedding Increases Anxiety-Like Behavior and Alters Hypothalamic-Pituitary-Adrenal Axis Function of Male BALB/cJ Mice

Maternal Separation Combined With Limited Bedding Increases Anxiety-Like Behavior and Alters Hypothalamic-Pituitary-Adrenal Axis Function of Male BALB/cJ Mice

Impact of Early Life Stress on Reward Circuit Function and Regulation

Oxytocin as an adolescent treatment for methamphetamine addiction after early life stress in male and female rats

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