---
title: "Prenatal alcohol plus cannabinoid exposure increases adult ethanol-seeking and alters mPFC CNR1 by"
id: "biorxiv-7-prenatal-alcohol-and-cannabinoid-co-exposure-increases-ethanol-seeking-in-adult"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-7-prenatal-alcohol-and-cannabinoid-co-exposure-increases-ethanol-seeking-in-adult"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.21.753297v1?rss=1"
published_at: "2026-09-23T09:50:14.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Prenatal alcohol plus cannabinoid exposure increases adult ethanol-seeking and alters mPFC CNR1 by
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-7-prenatal-alcohol-and-cannabinoid-co-exposure-increases-ethanol-seeking-in-adult
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.21.753297v1?rss=1)
- **Published At:** 2026-09-23T09:50:14.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Study in C57BL/6J mice evaluated effects of prenatal exposure to ethanol vapor (ALC), a cannabinoid agonist CP-55,940 (CB), both (ALC+CB), or neither (CON) on adult alcohol-related behaviors and cannabinoid-system proteins. - Gestational exposure occurred on gestational days 12–15; adult behavioral testing began on postnatal day 200. - Behavioral assays included home-cage ethanol drinking (N=108), operant self-administration, progressive-ratio schedules, extinction, and reinstatement testing (N=96). - Protein abundance of **CNR1** and CNRIP1 was measured in the **medial prefrontal cortex (mPFC)** and dorsomedial striatum (N=57) and correlated with within-subject drinking behaviors. - Prenatal **CB** exposure alone increased cumulative home-cage ethanol intake, with effects primarily evident in males. - Under a 40% ethanol progressive-ratio schedule, **ALC+CB** males consumed more than all other male groups; exposed females (ALC, CB, ALC+CB) consumed more than female controls. - **ALC+CB** males displayed greater extinction responding than all other male groups and greater reinstatement intake relative to baseline than CON and ALC males, indicating enhanced ethanol-seeking. - **ALC+CB** increased **mPFC CNR1** protein in males relative to all other groups; in females, CB and ALC+CB reduced mPFC CNR1. - Higher mPFC **CNR1** correlated with fixed-ratio and 40% progressive-ratio intake, extinction, and reinstatement measures, but these associations were exclusive to males. - Authors conclude prenatal co-exposure yields a persistent, male-specific phenotype of enhanced ethanol seeking associated with elevated mPFC **CNR1**, supporting further studies targeting corticostriatal cannabinoid signaling to reduce late-adult ethanol consumption. - This report is a preprint and has not been peer reviewed; additional methodological details beyond the abstract are not reported in the source provided.
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[ View ORCID Profile](http://orcid.org/0000-0002-5860-9308)Siara Kate Rouzer, Abigail Bowring, Aisley George, McKay Domen, Emma Labbe, Marisol Palacios, Rajesh Miranda doi: https://doi.org/10.64898/2026.09.21.753297 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. Siara Kate Rouzer Texas AM College of Medicine * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Siara%2BKate%2BRouzer%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Rouzer%20SK&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ASiara%2BKate%2BRouzer%2B) * [ORCID record for Siara Kate Rouzer](http://orcid.org/0000-0002-5860-9308 "Open in new tab") * For correspondence: srouzer@tamu.edu Abigail Bowring Texas AM College of Medicine * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Abigail%2BBowring%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Bowring%20A&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAbigail%2BBowring%2B) Aisley George Texas AM College of Medicine * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Aisley%2BGeorge%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=George%20A&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAisley%2BGeorge%2B) McKay Domen Texas AM College of Medicine * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=McKay%2BDomen%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Domen%20M&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AMcKay%2BDomen%2B) Emma Labbe Texas AM College of Medicine * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Emma%2BLabbe%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Labbe%20E&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AEmma%2BLabbe%2B) Marisol Palacios Texas AM College of Medicine * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Marisol%2BPalacios%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Palacios%20M&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AMarisol%2BPalacios%2B) Rajesh Miranda Texas AM College of Medicine * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Rajesh%2BMiranda%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Miranda%20R&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ARajesh%2BMiranda%2B) * [Abstract](https://www.biorxiv.org/content/10.64898/2026.09.21.753297v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5802697/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.09.21.753297v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5802697/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.09.21.753297v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5802697/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.09.21.753297v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5802697/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.09.21.753297v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5802697/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Background: Alcohol and cannabinoids are frequently used during pregnancy, however their combined effects on offspring outcomes are currently under-investigated. In this study, co-exposure was compared to single-drug and drug-free exposures for influences on adult alcohol-seeking and cannabinoid system proteomics. Methods: Pregnant C57BL/6J mice received ethanol vapor (ALC), CP-55,940 (0.75 mg/kg; CB), both (ALC+CB), or neither on gestational days 12-15. Beginning on Postnatal Day 200, male and female offspring underwent home-cage ethanol drinking (N=108) and operant self-administration, progressive-ratio, extinction, and reinstatement testing (N=96). CNR1 and CNRIP1 protein abundance was quantified in the medial prefrontal cortex (mPFC) and dorsomedial striatum (N=57) and compared to within-subject drinking behaviors. Results: Prenatal CB exposure increased cumulative home-cage ethanol intake, primarily in males. At 40% ethanol under progressive-ratio schedules, ALC+CB males consumed more than all other male groups, whereas all exposed female groups consumed more than controls. ALC+CB males also showed greater extinction responding than all other male groups and greater reinstatement intake relative to baseline than CON and ALC males. ALC+CB increased mPFC CNR1 in males relative to all other groups, whereas CB and ALC+CB reduced mPFC CNR1 in females. Higher mPFC CNR1 was associated with fixed-ratio and 40% progressive-ratio intake, extinction, and reinstatement exclusively in males. Conclusions: Prenatal co-exposure produced a persistent male phenotype of enhanced ethanol seeking that was distinct from either exposure alone and accompanied by elevated mPFC CNR1. This behavioral and molecular convergence justifies future investigations manipulating corticostriatal cannabinoid signaling to attenuate exposure-induced ethanol consumption in late adulthood. ### Competing Interest Statement The authors have declared no competing interest. ## Funder Information Declared National Institute on Alcohol Abuse and Alcoholism, F32AA029866, K99AA032336, AA028406 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. 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Siara Kate Rouzer, Abigail Bowring, Aisley George, McKay Domen, Emma Labbe, Marisol Palacios, Rajesh Miranda bioRxiv 2026.09.21.753297; doi: https://doi.org/10.64898/2026.09.21.753297 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. Share This Article: Copy [![Twitter logo](https://www.biorxiv.org/sites/all/modules/highwire/highwire/images/twitter.png)](https://www.biorxiv.org/highwire_log/share/twitter?link=http%3A%2F%2Ftwitter.com%2Fshare%3Furl%3Dhttps%253A%2F%2Fwww.biorxiv.org%2Fcontent%2F10.64898%2F2026.09.21.753297v1%26text%3DPrenatal%2520alcohol%2520and%2520cannabinoid%2520co-exposure%2520increases%2520ethanol-seeking%2520in%2520adult%2520offspring%2520and%2520produces%2520sex-dependent%2520medial%2520prefrontal%2520cannabinoid%2520receptor%25201%2520expression. 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