# Anterior Cingulate Dysfunction in a PAE-AIE Combined Model During Protracted Abstinence

> **NIH NIH P50** · STATE UNIVERSITY OF NY,BINGHAMTON · 2024 · $266,054

## Abstract

PROJECT SUMMARY
MAIN 5
Alcohol consumption during early pregnancy is a common occurrence in our society. Unfortunately, prenatal
alcohol exposure increases the risk of onset of alcohol consumption to problematic levels earlier in
adolescence. Both prenatal and adolescence periods are critical windows for neurodevelopment and insults to
the developing nervous system, such as alcohol exposure, may dysregulate typical neurogenesis and synapse
formation, ultimately resulting in behavioral maladaptations such as augmented anxiety-like behavior and
pathological pain perception. The pain and the addiction circuit overlap with many mesocortical interactions.
The anterior cingulate cortex (ACC) is at the intersection of addiction and pain circuit and receives dopamine
projections from the ventral tegmental area. Dopamine in the ACC contributes to the excitation/inhibition
balance within layer 2/3 in the ACC and is affected by chronic ethanol exposure during adolescence in the
nucleus accumbens in a sex- and age of exposure-dependent manner. Interestingly however, changes in
cortical dopamine and the resulting shift in excitation/inhibition balance is unknown following prenatal ethanol
exposure (PAE), adolescent intermittent ethanol exposure (AIE), or double-hit with PAE+AIE exposure.
Therefore in Main Project 5, we will elucidate the effect of PAE alone, AIE alone, and the combination of the
two (PAE+AIE) on the interplay between dopamine and glutamate and the resulting changes in affective
behavior and mechanical nociception. Our overarching hypothesis is that PAE+AIE exposure synergistically
augments anxiety-like behaviors and mechanical allodynia in male and female rats via altered interactions
between glutamate and dopamine in the ACC. Specifically, in Aim 1 we will examine the excitability of
glutamate neurons and dopamine terminal excitability in the ACC during protracted abstinence from PAE, AIE,
and PAE+AIE exposures using electrophysiology and fast scan cyclic voltammetry (FSCV), respectively. We
predict that PAE+AIE with reduce glutamate and dopamine transmission significantly more than either PAE or
AIE alone. In Aim 2, we will determine the impact of subsequent ethanol exposure on overall neural activity
and glutamate and dopamine transmission in ACC layer 2/3 using electrophysiology and FSCV, respectively.
We expect to find a sensitized response to acute ethanol with respect to glutamate and dopamine transmission
in PAE+AIE exposed rats compared to rats with single (PAE or AIE) exposure. Finally, in Aim 3 we will
determine a causal link between ACC layer 2/3 neuron activity and/or dopamine and anxiety-like behavior and
mechanical allodynia using chemogenetics. We predict that dysregulation in both glutamate and dopamine will
contribute to the pathological pain perception and augmented anxiety-like behavior in PAE+AIE exposed rats.
Collectively, this proposal will identify the impact of alcohol exposure during two developmentally critical
wind...

## Key facts

- **NIH application ID:** 10740451
- **Project number:** 2P50AA017823-16
- **Recipient organization:** STATE UNIVERSITY OF NY,BINGHAMTON
- **Principal Investigator:** Marvin Rafael Diaz
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $266,054
- **Award type:** 2
- **Project period:** 2009-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10740451

## Citation

> US National Institutes of Health, RePORTER application 10740451, Anterior Cingulate Dysfunction in a PAE-AIE Combined Model During Protracted Abstinence (2P50AA017823-16). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10740451. Licensed CC0.

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