Antenatal maternal stress alters functional brain responses in adult offspring during conditioned fear

Abstract

Antenatal maternal stress has been shown in rodent models and in humans to result in altered behavioral and neuroendocrine responses, yet little is known about its effects on functional brain activation. Pregnant female rats received a daily foot-shock stress or sham-stress two days after testing plug-positive and continuing for the duration of their pregnancy. Adult male offspring (age 14 weeks) with and without prior maternal stress (MS) were exposed to an auditory fear conditioning (CF) paradigm. Cerebral blood flow (CBF) was assessed during recall of the tone cue in the nonsedated, nontethered animal using the 14 C-iodoantipyrine method, in which the tracer was administered intravenously by remote activation of an implantable minipump. Regional CBF distribution was examined by autoradiography and analyzed by statistical parametric mapping in the three-dimensionally reconstructed brains. Presence of fear memory was confirmed by behavioral immobility ('freezing'). Corticosterone plasma levels during the CF paradigm were measured by ELISA in a separate group of rats. Antenatal MS exposure altered functional brain responses to the fear conditioned cue in adult offspring. Rats with prior MS exposure compared to those without demonstrated heightened fear responsivity, exaggerated and prolonged corticosterone release, increased functional cerebral activation of limbic/paralimbic regions (amygdala, ventral hippocampus, insula, ventral striatum, nucleus acumbens), the locus coeruleus, and white matter, and deactivation of medial prefrontal cortical regions. Dysregulation of corticolimbic circuits may represent risk factors in the future development of anxiety disorders and associated alterations in emotional regulation.

Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats

“…A wealth of evidence has correlated prenatal stress effects in the BLA with elevated anxiety-like behavior (Buss et al, 2012; Cratty et al, 1995; Kraszpulski et al, 2006; Sadler et al, 2011). Furthermore, prenatal stress alters amygdala neuron excitability (Ehrlich et al, 2015) and gene expression related to GABA (Laloux et al, 2012; Sarro et al, 2014), an inhibitory neurotransmitter that tightly regulates amygdala function and affective state (Ehrlich et al, 2009; Quirk and Gehlert, 2003; Rainnie et al, 2004).…”

Prenatal Stress Alters the Development of Socioemotional Behavior and Amygdala Neuron Excitability in Rats

“…Adult amygdala function and emotional behavior are altered by PS (Weinstock, 2008;Sadler et al, 2011), and several studies have identified effects of PS on the developing amygdala (Kraszpulski et al, 2006;Laloux et al, 2012). However, no study to date has described how PS influences the developmental trajectory of amygdala function or characterized the effects of PS on amygdala neurophysiology, regardless of age.…”

Effects of prenatal chronic mild stress exposure on hippocampal cell proliferation, expression of GSK‐3α, β and NR2B in adult offspring during fear extinction in rats

“…These studies found that prenatal stress induced learning and memory deficits in adult offspring (Green et al, 2011; Griffin et al, 2003; Matrisciano et al, 2013) which provide support evidence for our results. For example, a recent study demonstrated that animals, whose mother suffered acute stress (footshock), showed greater fear behavior during training and recall of fear conditioning (Sadler et al, 2011). However, our study was the first time to demonstrate that PNS impairs the extinction learning of adult offspring, which provides further support for the notion that maternal stress during pregnancy may be a risk factor for the development of fear or anxiety‐related disorders.…”

“…However, very little research has investigated how gestational stress influences the fear learning and memory in the offspring. Recent research found that animals whose mother suffered acute stress (foot shock) showed greater fear behavior during training and recall of fear conditioning (Sadler et al, 2011). Both the brain noradrenergic systems and the hypothalamic–pituitary–adrenal (HPA) axis are thought to be involved in regulating the cognitive processes such as learning and memory (de Quervain et al, 2009), including specifically conditioned fear and extinction learning (McIntyre et al, 2002).…”