A single episode of stress during adolescence impairs short-term memory and increases risk behaviour in an animal model of attention-deficit/hyperactivity disorder

https://doi.org/10.1016/j.beproc.2021.104395Get rights and content

Highlights

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    Spontaneously hypertensive rats (SHR) are a validated animal model of ADHD.

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    A single episode of stress during adolescence increases risk behaviour in adult SHR.

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    A single episode of stress during adolescence impairs short-term memory in adult SHR.

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    A single episode of stress can lead to long-term behavioural changes in a rat model of ADHD.

Abstract

Adolescence is a period of increased sensitivity to stress and vulnerability to the manifestation of psychiatric disorders, such as attention-deficit/hyperactivity disorder (ADHD). Nevertheless, the relationship between stress during adolescence and ADHD is still unclear. Knowing that stress can have long-term consequences, the aim of this study was to evaluate the impact of a single episode of restraint stress during adolescence on locomotion, risk behaviour and short-term memory in adult spontaneously hypertensive rats (SHR), a validated animal model of ADHD. A single episode of stress during adolescence increased risk behaviour and impaired short-term recognition memory, but did not alter locomotion in adult SHR. These findings show that stress during adolescence, even acute, may lead to long-term behavioural consequences in an animal model of ADHD.

Introduction

During adolescence several morphofunctional changes occur in the brain, such as remodeling of cortical and limbic regions, as well as neuroendocrine shifts (Casey et al., 2008; Ojeda and Terasawa, 2002; Sowell et al., 1999). In addition, during this stage of development, cortical maturation occurs later than maturation of limbic regions (Davey et al., 2008), making adolescence a period of vulnerability for manifestation of psychiatric disturbances (Paus et al., 2008), such as attention-deficit/hyperactivity disorder (ADHD) (Sowell et al., 2003).

Attention-deficit/hyperactivity disorder is one of the most prevalent psychiatric disorders worldwide, affecting about 7.2 % of children (Thomas et al., 2015) and 2.5 % of adults (Simon et al., 2009). This disorder is characterized by symptoms of inattention and/or hyperactivity-impulsivity (American Psychiatric Association, 2013).There is a bidirectional relationship between stress and ADHD, since ADHD is associated with a greater risk for stressful life events, and, concomitantly, high-stress exposure mainly in childhood can predict ADHD persistence into adulthood (Friedrichs et al., 2012; Hartman et al., 2019; Vrijsen et al., 2018). Accordingly, some studies have also shown that stress during early developmental periods (e.g. maternal separation) is associated with ADHD-like behaviours in rodents, i.e. hyperactivity, inattention, and impulsivity (Bock et al., 2017; Colorado et al., 2006; Kwak et al., 2009). Nevertheless, the relationship between stress during adolescence and ADHD is still unclear. Therefore, knowing that stress during adolescence can have long-term consequences (Romeo and McEwen, 2006), the aim of this study was to evaluate whether a single episode of stress during adolescence would lead to behavioural changes in adult spontaneously hypertensive rats (SHR), one of the most used ADHD animal models (Russell, 2011).

Section snippets

Animals

Adolescent male inbred SHR/NCrl strain rats (n = 14) at postnatal day (PND) 30 were used. Adolescence in rats takes place from PND 28–42, and adulthood from PND 60 when sexual maturity occurs (Spear, 2000). After weaning (PND 21), groups of two or three animals per plastic box (40 × 33 × 17 cm) were kept in the institutional animal care facility in a constant temperature room (22 ± 2 °C), on a standard 12‐hour light/dark cycle (lights on at 07:00 am), with access to water and chow ad libitum.

Risk behaviours and locomotion

Restraint stress had no significant effect on the percentage of time spent in open arms (Ctrl: 29.32 ± 8.61 vs RS: 43.09 ± 11.53, p = 0.357; Fig. 2a) or the percentage of entries in open arms of EPM (Ctrl: 37.67 ± 7.46 vs RS: 43.1 ± 9.32, p = 0.657; Fig. 2b), as well as number of entries in enclosed arm entries (Ctrl: 4.29 ± 0.42 vs RS: 5.0 ± 0.79, p = 0.439; Fig. 2c). In the OF test, rats from the RS group spent more time (Ctrl: 37.29 ± 8.13 vs RS: 80.5 ± 13.65, p = 0.019; Fig. 2d) and had a

Discussion

Adolescence is a period of increased sensitivity to stress, due to hyper-reactivity of the hypothalamic-pituitary-adrenal (HPA) axis that occurs during this phase of development (Eiland and Romeo, 2013; Romeo, 2010a, 2010b). Studies with animal models have shown that stress during adolescence can have consequences that extend into adult life, including a lower level of "resilience" to stressful events (i.e. a higher HPA axis activation in response to a novel stressor agent) (Isgor et al., 2004;

CRediT authorship contribution statement

Ícaro Raony: Validation, Formal analysis, Investigation, Data curation, Writing - original draft. Arnaldo Geraldo: Conceptualization, Methodology, Investigation. Pablo Pandolfo: Conceptualization, Methodology, Resources, Writing - review & editing, Supervision, Project administration, Funding acquisition.

Declaration of Competing Interest

All the authors declare that they have no conflicts of interest.

Acknowledgements

This research was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq - 430746/2016-4) and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ - E-26/203.284/2016). They had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The authors are grateful to Dr. Norman Arthur Ratcliffe for reviewing the manuscript.

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