Exposure to Chronic Mild Stress Differentially Alters Corticotropin‐Releasing Hormone and Arginine Vasopressin mRNA Expression in the Stress‐Responsive Neurocircuitry of Male and Female Rats Prenatally Exposed to Alcohol

Abstract

Background Prenatal alcohol exposure (PAE) results in dysregulation of the offspring hypothalamic-pituitary-adrenal (HPA) axis, increasing sensitivity to stressors and vulnerability to stress-related disorders. We have previously shown that exposure to chronic mild stress (CMS) in adulthood significantly increases anxiety-like behaviors (elevated plus maze) in PAE males and females compared to controls. To explore neurobiological mechanisms linking HPA dysregulation and altered anxiety-like behavior, we investigated neuropeptide [corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP)] expression in brain areas involved in the stress neurocircuitry of animals from this previous behavioral study. Methods Adult PAE, pair-fed (PF), and ad-libitum fed control (C) male and female offspring exposed to CMS or remaining undisturbed (Non-CMS) were terminated 30 min following behavioral testing. Results In the paraventricular nucleus, CMS increased CRH mRNA levels in PAE compared to PF and C males, and increased AVP mRNA levels in PAE compared to C males, with no differential effects for CRH or AVP in females. In the central nucleus of the amygdala, there was an increase in CRH mRNA expression overall, regardless of CMS condition or sex, in PAE compared to C animals. Moreover, in PF males, CMS increased AVP mRNA levels in the paraventricular nucleus, resulting in a decreased CRH/AVP ratio compared to PAE males, and decreased amygdala CRH mRNA compared to that in the Non-CMS condition. Conclusions CMS differentially altered central HPA peptide expression in PAE and PF animals compared to their control counterparts, with a possible shift toward greater CRH mediation of HPA regulation in PAE males, and greater AVP mediation of HPA regulation in PF males. However, changes in CRH and AVP expression do not align fully with the anxiogenic profile observed in our previous behavior study, suggesting that other neuronal substrates and limbic forebrain regions also contribute to increased anxiety-like behavior following CMS.

Dipyrone ameliorates behavioural changes induced by unpredictable chronic mild stress: gender differences

“…Bowman et al [35] suggested that sex differences must be taken into account when investigating or describing stress and associated squeal according to their study on chronic stress effects on memory. Similar results revealing gender-related variability in vulnerability to UCMS treatment and activity of antidepressants have been demonstrated in the literature [36,37].…”

Short- and long-term effects of stress during adolescence on emotionality and HPA function of animals exposed to alcohol prenatally

“…Indeed, PAE reduced CRHR1 expression in the medial amygdala of adult males and females, reduced CRHR1 expression in the basolateral amygdala of adult females, and reduced CRHR1 expression in the anterior cingulate and prelimbic cortices of adult males. PAE-induced reduction of CRHR1 expression in the basolateral and medial amygdala in adulthood may be a compensatory response to the increase in CRH mRNA expression in the central amygdala observed in adult PAE animals (Lan et al, 2015). Indeed, while CRH is produced in the central amygdala, the central amygdala contains very few CRHR1 receptors, which are present in abundance in the basolateral and medial amygdala (Van Pett et al, 2000).…”

“…Using a rat model of PAE, we have demonstrated that PAE rats exposed to chronic, unpredictable but mild stressful experiences in adulthood show increased anxiety- and depressive-like behaviors, and do so in a sexually dimorphic manner (Hellemans et al, 2008, 2010a,b). These behavioral alterations are associated with functional and structural changes in brain areas underlying stress and emotional regulation, including the medial prefrontal cortex (mPFC) and amygdala (Lan et al, 2015; Raineki et al, 2014; Uban et al, 2013). However, little is known about how exposure to stressful environments during adolescence may further alter the developmental trajectory of key brain areas such as the mPFC and amygdala, and potentially contribute to the disproportionally high rate of psychopathologies following PAE.…”

Sex differences: Transcriptional signatures of stress exposure in male and female brains

“…101 However, not surprisingly, not every work published agrees. 136,137 Other regions involved in the stress circuitry such as the CeA and basolateral amygdala (BLA), as well as the bed nucleus of the stria terminalis (BNST) show the different extent of sex-specific regulation of such genes and others, including the Bdnf cascade [137][138][139][140] (Tables 3 and 4).…”