# Simultaneous prenatal alcohol and cannabinoid exposure & offspring corticostriatal neurocircuitry

> **NIH NIH F32** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2024 · $63,970

## Abstract

PROJECT SUMMARY
Prenatal alcohol exposure (PAE) is the most common cause of developmental disorders, though concurrent
exposure to other psychoactive substances may exacerbate adverse outcomes. Recent preference for
simultaneous use of alcohol and cannabis (SAC) among young adults of child-bearing age combined with early
preclinical evidence for synergistic developmental harm, support a premise for investigating SAC as a specific
developmental source of disability. Despite indications that both PAE and prenatal cannabinoid exposure (PCE)
alter endocannabinoid signaling through cannabinoid receptor 1 (CNR1) in offspring, it is yet unknown whether
impairments to CNR1 – a receptor essential to healthy fetal neurodevelopment – underly impairments associated
with SAC. Notably, PAE impairs CNR1-regulated synaptic transmission from striatal-projecting cortical neurons.
In drug-naïve mice, impaired striatal CNR1-regulated activity contributes to motor dysfunction, hyperactivity and
increased drug-seeking behaviors, deficits observed in humans with PAE and PCE. Therefore, the objective of
this proposal is to investigate the impact of SAC on CNR1-associated neural circuits and behaviors in exposed
offspring. Preliminary data from our lab have shown that a CNR1-associated gene network that regulates striatal
synaptic activity is changed by acute fetal ethanol exposure, and combined SAC exposure augments growth
deficits in neural stem cells from single-drug and drug-free exposures. Collectively, the literature and these data
inform our central hypothesis that SAC offspring will exhibit impaired CNR1-linked synaptic mechanisms within
the striatum corresponding with increased motor deficits and drug-seeking behaviors.
We will test this hypothesis in the following aims: Specific Aim 1) To assess SAC-induced changes in genes
that regulate corticostriatal synaptic activity. We will use integrative RNAseq and ATAC-seq to investigate a pre-
determined gene network associated with CNR1-regulated corticostriatal synaptic plasticity in prenatally
exposed offspring. Specific Aim 2) To assess whether SAC augments behavioral deficits and striatal protein
expression. We will perform a battery of behavioral assays investigating native deficits in motor function and
ethanol-seeking behaviors in prenatally exposed offspring. We will compare behavioral deficits with striatal
protein expression using sandwich ELISAs, quantifying CNR1 and endogenous cannabinoid ligands
anandamide and 2-arachidonylglycerol. Prenatal drug exposure will occur from gestational days 12-15, a period
of peak neurogenesis for corticostriatal neurons, and will incorporate vaporized ethanol inhalation and i.p
administration of synthetic cannabinoid CP-55940. Successful completion of this proposal will identify specific
mechanistic changes underlying SAC, a translationally-relevant but under-investigated form of prenatal drug
exposure, and inform future targets for therapeutic intervention. Furthermore, t...

## Key facts

- **NIH application ID:** 10818481
- **Project number:** 5F32AA029866-03
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** Siara Rouzer
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $63,970
- **Award type:** 5
- **Project period:** 2022-05-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10818481

## Citation

> US National Institutes of Health, RePORTER application 10818481, Simultaneous prenatal alcohol and cannabinoid exposure & offspring corticostriatal neurocircuitry (5F32AA029866-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10818481. Licensed CC0.

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