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Sex differences in alcohol‐induced HPA activation following systemic vs icv administration in rats: Neuronal activation studies
Author(s) -
Davis Seth,
Wakley Alexa A.,
Yap Parry,
Pham Charleen,
Kiester Christopher,
Selvage Dan John
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1265.4
Subject(s) - parvocellular cell , endocrinology , medicine , estrous cycle , hypothalamus , stimulation , hormone , immediate early gene , c fos , biology , gene expression , biochemistry , gene
Understanding how alcohol differentially affects the hypothalamic‐pituitary‐adrenal (HPA) axis in males vs. females is important for the development of sex‐specific pharmacological treatments for alcohol abuse. Using intracerebroventricular (icv) administration, our lab previously reported that alcohol activated the hypothalamic‐pituitary‐adrenal (HPA) axis of rats in a sex‐ and estrous cycle‐ dependent manner. This effect was greatest in females in stages of the estrous cycle when the effects of estradiol (E2) are high (proestrus and estrus), as these animals showed greater levels of HPA‐ linked hormonal and neuronal activation by alcohol compared to males and to females in stages of the cycle when E2 levels are low (diestrus I and II). For the current study, we used an intraperitoneal (i.p.) alcohol injection to determine if systemic alcohol activates neuronal HPA activity in a similar manner as centrally delivered alcohol, or whether the many non‐CNS specific effects of the drug in the periphery affect its ability to cause sexually dimorphic activation of the HPA axis. Relative neuronal stimulation levels were determined using single‐ and dual‐ labeling immunofluouresence (IF) staining of the transcription factor and marker of neuronal activity c‐fos (Fos) in the medial parvocellular and magnocellular areas of the paraventricular nucleus of the hypothalamus (PVN), which is known to regulate HPA function. As with icv administration, systemic alcohol induced Fos expression in the medial parvocellular PVN, where cell bodies for corticotropin releasing factor (CRF), the main driver of HPA activation reside. Significant Fos expression was also stimulated in the magnocellular PVN, where cell bodies for arginine vasopressin (AVP), which contributes to HPA activation by CRF, are located. Unlike our results using icv administration, females receiving systemic alcohol exhibited less alcohol‐ induced medial parvocellular PVN Fos than males, with this difference reaching significance in diestrous females. Alcohol also induced less AVP‐ associated magnocellular PVN Fos in females than males following systemic alcohol injection, again with the greatest difference being between males and diestrous females. These results indicate that non‐ CNS specific effects of alcohol in the periphery contribute to HPA responsiveness to the drug in a sexually dimorphic manner, with the male HPA axis exhibiting a significantly greater reactivity to systemic injection of the drug than diestrous females. Support or Funding Information NIH R01 AA016947‐01A1