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Adolescent chronic unpredictable stress leads to increased anxiety and attention deficit/hyperactivity-like symptoms in adulthood

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Abstract

Background

Early-life adversities during development (e.g., child abuse and neglect) are linked to multiple behavioral and cognitive dysfunctions, such as attention deficit/hyperactivity disorder (ADHD) and anxiety disorders, which have high comorbidity. However, the impact of adversities during adolescence, a crucial period in early life for these disorders, is understudied. Using a chronic unpredictable stress (CUS) model in rats, we investigated whether adversities in adolescence could lead to increased anxiety and ADHD-like symptoms in adulthood.

Methods

Mid- to late-adolescent (5–7-week-old) male and female Sprague–Dawley rats underwent a mild CUS procedure for 2 weeks. Various stressors were applied in an unpredictable way. Rats of both sexes were then trained with a 2-choice reaction time (2-CRT) task during adulthood, which are designed to detect ADHD-like symptoms, including increased impulsivity and lapse of attention. In addition, an open field test was conducted to examine if CUS resulted in a persistent increase in anxiety-like behavior during adulthood.

Results

Both male and female rats with CUS exposure travelled shorter distances in the open field and spent less time in the center zone, indicating increased anxiety. In the 2-CRT task, rats of both sexes with CUS exposure showed increased impulsivity. Augmented lapses of attention were observed in female but not male rats.

Conclusion

Chronic unpredictable stress during adolescence increases anxiety and leads to ADHD-like symptoms in both male and female rats in adulthood. The deficits are more severe in females than in males. These observations support that adversities during adolescence persistently increase anxiety, which is comorbid with attention deficits.

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Acknowledgements

The authors thank Mark Kogutowski for his technical support.

Funding

This work was supported by the National Institutes of Health (Grant AA026421 to RS).

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  1. Francis Kwarteng and Ruixiang Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Jacob School of Medicine and Biomedical Sciences, University at Buffalo, 1021 Main Street, Buffalo, NY, 14203, USA

    Francis Kwarteng, Ruixiang Wang, Veronika Micov, Kathryn A. Hausknecht, Marisa Turk, Keita Ishiwari, Saida Oubraim, An-Li Wang, Jerry B. Richards, Samir Haj-Dahmane & Roh-Yu Shen

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  1. Francis Kwarteng
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Kwarteng, F., Wang, R., Micov, V. et al. Adolescent chronic unpredictable stress leads to increased anxiety and attention deficit/hyperactivity-like symptoms in adulthood. Psychopharmacology 239, 3779–3791 (2022). https://doi.org/10.1007/s00213-022-06242-1

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