Evidence map›Paper›PMID 40582636›Full record

ArticleNeuropharmacology2025

Perinatal fentanyl exposure drives enduring addiction risk and central amygdala gene dysregulation.

Courtney P Wood, Yeji Shin, Maria G Balaguer, Paola Campo, Selen Dirik, Bryan A Montoya, Gregory M R Cook, Gabrielle M Palermo, Parsa K Naghshineh, Alex Morgan and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuropharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Courtney P WoodDepartment of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA.
Yeji ShinDepartment of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA.
Maria G BalaguerDepartment of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA.
Paola CampoDepartment of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA.
Selen DirikDepartment of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA.
Bryan A MontoyaDepartment of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA.
Gregory M R CookDepartment of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA.
Gabrielle M PalermoDepartment of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA.
Parsa K NaghshinehDepartment of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA.
Alex MorganDepartment of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA.
Sara R M U RahmanDepartment of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA.
Abraham A PalmerDepartment of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA; Institute for Genomic Medicine, University of California San Diego, School of Medicine, La Jolla, CA, USA.
Francesca TeleseDepartment of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA.
Giordano de GuglielmoDepartment of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA. Electronic address: gdeguglielmo@health.ucsd.edu.

Funding

DP30DA060810 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Abraham A Palmer · 2024 to 2026
$5.6M
Multiomic profiling of cell types mediating opioid use disorder in ratsR01DA056602 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Giordano De Guglielmo, Francesca Telese · 2022 to 2026
$3.0M
NIDA NIH HHS P30 DA060810NIDA NIH HHS R01 DA056602
6 · The paper itself

Abstract

The use of fentanyl and other opioids during pregnancy is a pressing public health issue due to its association with Neonatal Opioid Withdrawal Syndrome (NOWS) and long-term neurobehavioral deficits. Human epidemiologic studies are confounded by both genetic and environmental factors that differ between exposed and unexposed children. We developed a novel rat model of perinatal fentanyl exposure in heterogeneous stock (HS) rats characterized by high genetic diversity, to investigate NOWS symptoms and its long-term effects on adult fentanyl self-administration, drug-seeking behavior, and central amygdala (CeA) transcriptomic changes, addressing a critical gap in understanding synthetic opioid impacts. Offspring born to fentanyl-exposed dams exhibited reduced survival, lower body weight, spontaneous withdrawal symptoms, and mechanical hypersensitivity during adolescence. These rats displayed negative affect in adolescence, while they showed increased fentanyl self-administration, heightened drug-seeking during reinstatement, and elevated corticosterone levels during withdrawal in adulthood. To explore the molecular underpinnings of these physiological and behavioral outcomes, we conducted RNA-seq in the CeA of adult rats, revealing dysregulated pathways related to GPCR signaling, adaptive immune response and neurodevelopmental processes. These transcriptional changes provide insights into the mechanisms driving addiction vulnerability and stress-related behaviors following early fentanyl exposure. Our findings highlight the lasting impact of perinatal opioid exposure in an experimental system that avoids many of the confounds that plague studies in humans, underscoring the need for preclinical models to study NOWS and its long-term consequences. This model offers translational relevance for developing therapeutic strategies to mitigate NOWS and reduce neuropsychiatric risks associated with perinatal opioid exposure.

Indexed as

Analgesics, OpioidCentral Amygdaloid NucleusFentanylOpioid-Related DisordersPrenatal Exposure Delayed EffectsAnimalsDrug-Seeking BehaviorFemaleMalePregnancyRatsSelf AdministrationSubstance Withdrawal SyndromeAnalgesics, OpioidFentanylAddiction vulnerabilityCentral amygdalaNeonatal opioid withdrawal syndromePerinatal fentanylRat modelTranscriptomics

Identifiers

PMID40582636
PMCPMC12377289

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.