Exposure to variable prenatal stress in rats: Effects on anxiety-related behaviors, innate and contextual fear, and fear extinction

Abstract

Rats repeatedly exposed to variable prenatal stress (PNS) exhibit behavioral features often observed in neuropsychiatric disorders including elevated sensitivity to stimulants and impairments of attention, inhibitory control and memory-related task performance. However, to date there have been relatively few studies designed to assess the effects of PNS on anxiety, stress and fear responses, or the function of the hypothalamic-pituitary-adrenal (HPA) axis (a system clearly linked to stress and fear-related responses as well as neuropsychiatric disorders). In the current study, rats exposed to variable PNS were evaluated for anxiety-related behaviors in open field, elevated plus maze, and light/dark preference tasks. Innate fear responses were assessed using a predatory odor task and learned fear and extinction were assessed with a contextual fear conditioning task. As an indicator of HPA axis function, serum corticosterone levels were determined by enzyme immunoassay at various time points. The results indicated that PNS resulted in several behavioral anomalies including decreased innate fear responses to predator odor, impaired fear extinction, increased locomotor activity and stereotypic-like behaviors. Baseline levels of corticosterone in PNS subjects were similar to non-stressed controls; however, when exposed to acute stress, they exhibited an increase in corticosterone that was greater in magnitude. PNS was not associated with increased anxiety-like behaviors or deficits in learning or retention during contextual fear conditioning. Collectivity, these data support the argument that variable PNS in rats is a valid model system for studying some behavioral components of neuropsychiatric disorders as well as the influence of stress hormones.

Prenatal glucocorticoid exposure in rats: programming effects on stress reactivity and cognition in adult offspring

“…There was no effect of prenatal glucocorticoid exposure on baseline CORT levels in our study, consistent with some previous results (Wilson et al, 2013). However, this does not exclude an effect on HPA axis activity, since one of the best-characterized deficits in HPA axis regulation induced by prenatal stress is the negative feedback control of stress-induced hormone responses (Vallee et al, 1997;Wilson et al, 2013). Additional assessment of HPA axis responses to stress, measurement of circulating ACTH and the temporal patterns of activation and termination of HPA hormone secretion after repeated exposure to stress (Fride et al, 1986) would provide further insight into longterm effects in this model.…”

“…Thus, this animal model may provide a laboratory tool to study the mechanisms underlie this link. There was no effect of prenatal glucocorticoid exposure on baseline CORT levels in our study, consistent with some previous results (Wilson et al, 2013). However, this does not exclude an effect on HPA axis activity, since one of the best-characterized deficits in HPA axis regulation induced by prenatal stress is the negative feedback control of stress-induced hormone responses (Vallee et al, 1997;Wilson et al, 2013).…”

“…Although similar negative findings have been reported by others (Wilson et al, 2013), our results contrast with a previous study using the same animal model . The reasons for this are unclear but may include differences in experimental conditions, such as the use of different experimental apparatus and the setting (these experiments were performed in a different animal facility).…”

“…In rodents, prenatal stress programs hypersensitivity to stress, including heightened hypothalamicpituitary-adrenal (HPA) axis activity (Vallee et al, 1997;Wilson et al, 2013) and increased fear and anxiety-like behavior (Takahashi et al, 1992;Vallee et al, 1997;Wakshlak & Weinstock, 1990;Welberg et al, 2001). Prenatal stress also affects cognition as demonstrated by impaired spatial learning and memory (Brabham et al, 2000;Lemaire et al, 2000;Markham et al, 2010;Son et al, 2006;Yang et al, 2006), working memory (Gue et al, 2004;Markham et al, 2010) and cued and contextual fear conditioning and extinction (Green et al, 2011;Markham et al, 2010;Wilson et al, 2013). …”

Long-term effects of maternal exposure to surgical stress at the earliest stage of pregnancy on blood pressure and behavior in offspring of OXYS rats

“…В соответствии с гипотезой DOHaD (Developmental Origin of Health and Disease) стресс и другие негативные воздействия на мать во время беременности вызывают долгосрочные послед-ствия, такие как задержка роста, гипертония и инсулин-независимый диабет в постнатальный период (Barker, 2000). Исследование воздействия пренатального стресса на поведение будущих потомков, в частности повышение у них уровня тревожности, показано в работах (Wilson et al, 2013;Said et al, 2015;Badache et al, 2017).…”