Behavioural Brain Research 399 (2021) 113026 Available online 25 November 2020 0166-4328/© 2020 Elsevier B.V. All rights reserved. Anxiety-like behavior and neuroendocrine changes in offspring resulting from gestational post-traumatic stress disorder Luana A. Chagas a , Tatiane H. Batista a , Ana Cl´ audia A.F. Ribeiro a , Mariela S. Ferrari a , J´ adina S. Vieira a , Viviana C.T. Rojas a , Bruna Kalil-Cutti a , Lucila L.K. Elias b , Alexandre Giusti-Paiva a , Fabiana C. Vilela a, * a Instituto de Ciˆ encias Biom´ edicas, Universidade Federal de Alfenas, Alfenas, Brazil b Departmento de Fisiologia, Faculdade de Medicina de Ribeir˜ ao Preto, Universidade de S˜ ao Paulo, Brazil A R T I C L E INFO Keywords: PTSD Perinatal Anxiety Corticosterone ABSTRACT Exposure to stressful environmental events during the perinatal period can increase vulnerability to psychopa- thologies that cause neuroendocrine changes associated with defcits in emotional behavior that can appear early in life. Post-traumatic stress disorder (PTSD) is a frequent, chronic, and disabling disorder that negatively im- pacts the emotional, social, and cognitive behaviors of affected individuals. Thus, we induced PTSD in pregnant rats by applying inescapable footshocks and then investigated the behavioral parameters similar to anxiety in offspring at prepubertal age, in addition to the plasma levels of maternal and offspring corticosterone and expression of glucocorticoid receptors (GR) in the offspring’s hippocampus. With the dams, maternal behavior, open feld, and object recognition tests were performed. With the male and female offspring, we performed the following: quantifcation of ultrasonic vocalizations, elevated plus-maze test, evaluation of exploratory activity in the open feld, and hole board test, as well as plasma corticosterone measurements and Western blotting for GR. Our results showed that gestational PTSD affected maternal behavior, led to anxiety-like symptoms, increased corticosterone levels, and increased GR expression in the offspring’s hippocampus. Therefore, our data can contribute to the understanding of the onset of early (childhood and juvenile/pre-pubertal phases) anxiety owing to exposure to a traumatic event during the gestation period. 1. Introduction Perinatal stress adversely affects human development, increasing susceptibility to diseases later in life as well as altering behavioral development [1–4]. Thus, exposure to stressful environmental events during the perinatal period can increase vulnerability to psychopathol- ogies that cause neuroendocrine changes associated with defcits in emotional behavior that in turn can appear early in and persist throughout life [5,6]. Beginning with the prenatal period and the start of postnatal life, the brain is still developing and is highly sensitive to the infuence of positive and negative external experiences [7,8]. According to an estimate, 20 % of pregnant women experience perinatal stress and depression [9], approximately 3.3 % of pregnant women have post-traumatic stress disorder (PTSD), and 4% of women have postpartum PTSD. The impact of maternal PTSD during the peri- natal period on descendants has not been examined comprehensively [10]. PTSD is considered a psychiatric disorder triggered by a traumatic experience or event. This disorder is considered a frequent, chronic, and disabling disorder that negatively impacts the emotional, social, and cognitive behaviors of affected individuals [11,12]. Thus, we induced PTSD in pregnant rats and investigated behavioral parameters similar to anxiety in the offspring at prepubertal age. To induce PTSD in this study, we exposed pregnant rats to a series of inescapable footshocks paired with a PTSD risk factor, that is, social isolation. This is because this model has been considered capable of mimic at the same time both the cognitive and emotional features of the disorder using well-validated paradigms [11]. In rodents, the relation between perinatal stress and behavioral changes in offspring has been demonstrated. The offspring of rats exposed to variable stress during pregnancy show behaviors like anxi- ety. In addition, dams exposed to variable stress show elevated corti- costerone levels in their plasma, and their offspring, when exposed to * Corresponding author at: Instituto de Ciˆ encias Biom´ edicas, Universidade Federal de Alfenas, Avenida Jovino Fernandes Sales 2600, 37130-000, MG, Brazil. E-mail addresses: facvilela@gmail.com, fabiana.cardoso@unifal-mg.edu.br (F.C. Vilela). Contents lists available at ScienceDirect Behavioural Brain Research journal homepage: www.elsevier.com/locate/bbr https://doi.org/10.1016/j.bbr.2020.113026 Received 9 October 2020; Received in revised form 29 October 2020; Accepted 18 November 2020