# Prenatal Alcohol and Anxiety: An Ontogenetic Role for CRF

> **NIH NIH R01** · STATE UNIVERSITY OF NY,BINGHAMTON · 2021 · $347,094

## Abstract

Abstract
Alcohol drinking and alcohol abuse during pregnancy is surprisingly high which can lead to a spectrum of
deficits in offspring termed Fetal Alcohol Spectrum Disorders. One of the most common consequences of
prenatal alcohol exposure (PAE) is the emergence of anxiety disorders that are apparent in childhood and
persist through adulthood. Coincident and highly associated with anxiety is the prevalence of alcohol abuse in
individuals with PAE. Importantly, these observations are evident even following exposure to moderate levels
of ethanol – a common pattern of alcohol consumption in pregnancy. Despite compelling epidemiological data,
the neurobiological mechanisms underlying moderate PAE-induced anxiety are not well understood. The
actions of corticotropin-releasing factor (CRF) through its cognate receptor, CRF1R, are involved in alcohol
exposure-induced anxiety and alcohol preference in adult males, and their expression is altered by PAE in
anxiety-related brain structures. However, the developmental time-course of CRF1R function and how its
function is altered by PAE across ontogeny is unknown. We have recently characterized a model of moderate
PAE using a single exposure to vaporized ethanol on gestational day (G) 12, a developmental epoch during
which the amygdala begins to appear, that produces increased anxiety-like behaviors in adolescent male
offspring and affects emotional processing in adult males, with no apparent effects in females. Based on this,
we hypothesize that G12 PAE reduces CRF1R function through ontogeny, which contributes to the biphasic
anxiety phenotype and results in alterations in acute alcohol and CRF1R interactions. To test our hypothesis,
Aim 1 will determine the developmental time-course of CRF1R function within the central amygdala and its
relation to anxiety-like behaviors. Aim 2 will examine the impact of moderate G12 PAE on alterations to CRF1R
function within the central amygdala across development and into adulthood, as it contributes to PAE-induced
alterations in anxiety-like behavior. Finally, Aim 3 will test the effect of moderate G12 PAE on acute ethanol-
CRF1R interactions within the central amygdala and how CRF1R contribute to ethanol intake across ontogeny.
These innovative studies will test novel and unique hypotheses surrounding the long-term effects of moderate
PAE and describe neural mechanisms specific to deficits in anxiety-like behaviors and its association with
elevated ethanol intake in an age- and sex-specific manner.

## Key facts

- **NIH application ID:** 10210620
- **Project number:** 1R01AA028566-01A1
- **Recipient organization:** STATE UNIVERSITY OF NY,BINGHAMTON
- **Principal Investigator:** Marvin Rafael Diaz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $347,094
- **Award type:** 1
- **Project period:** 2021-06-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10210620

## Citation

> US National Institutes of Health, RePORTER application 10210620, Prenatal Alcohol and Anxiety: An Ontogenetic Role for CRF (1R01AA028566-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10210620. Licensed CC0.

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