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.
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.
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.
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.