Evidence map›Paper›PMID 39348003›Full record

ArticlePsychopharmacology2025

The ultrasonic vocalization (USV) syllable profile during neonatal opioid withdrawal and a kappa opioid receptor component to increased USV emissions in female mice.

Kelly K Wingfield, Teodora Misic, Kaahini Jain, Carly S McDermott, Nalia M Abney, Kayla T Richardson, Mia B Rubman, Jacob A Beierle, Sophia A Miracle, Emma J Sandago and 6 more

Abstract read
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In one paragraph

Article in Psychopharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Kelly K WingfieldLaboratory of Addiction Genetics, Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 140 The Fenway, Boston, MA, USA.
Teodora MisicLaboratory of Addiction Genetics, Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 140 The Fenway, Boston, MA, USA.
Kaahini JainLaboratory of Addiction Genetics, Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 140 The Fenway, Boston, MA, USA.
Carly S McDermottLaboratory of Addiction Genetics, Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 140 The Fenway, Boston, MA, USA.
Nalia M AbneyLaboratory of Addiction Genetics, Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 140 The Fenway, Boston, MA, USA.
Kayla T RichardsonLaboratory of Addiction Genetics, Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 140 The Fenway, Boston, MA, USA.
Mia B RubmanNIH/NIDA Summer Undergraduate Fellowship Program, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Jacob A BeierleT32 Biomolecular Pharmacology Training Program, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Sophia A MiracleLaboratory of Addiction Genetics, Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 140 The Fenway, Boston, MA, USA.
Emma J SandagoLaboratory of Addiction Genetics, Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 140 The Fenway, Boston, MA, USA.
Britahny M BaskinLaboratory of Addiction Genetics, Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 140 The Fenway, Boston, MA, USA.
William B LynchLaboratory of Addiction Genetics, Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 140 The Fenway, Boston, MA, USA.
Kristyn N BorrelliLaboratory of Addiction Genetics, Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 140 The Fenway, Boston, MA, USA.
Emily J YaoLaboratory of Addiction Genetics, Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 140 The Fenway, Boston, MA, USA.
Elisha M WachmanDepartment of Pediatrics, Boston University Chobanian & Avedisian School of Medicine, Boston Medical Center, Boston, MA, USA.
Camron D BryantLaboratory of Addiction Genetics, Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 140 The Fenway, Boston, MA, USA. c.bryant@northeastern.edu.ORCID http://orcid.org/0000-0003-4505-5809

Funding

A Reduced Complexity Cross in BALB/c substrains to identify the genetic basis of oxycodone dependence phenotypesU01DA050243 · NIDA · NORTHEASTERN UNIVERSITY · PI BRYANT, CAMRON D · 2020 to 2023
$3.3M
Systems genetics of premorbid and cocaine use traits in a rat reduced complexity crossU01DA055299 · NIDA · NORTHEASTERN UNIVERSITY · PI BRYANT, CAMRON D, KANTAK, KATHLEEN M. · 2022 to 2025
$2.8M
Training Program on Development of Medications for Substance Use DisorderT32DA055553 · NIDA · NORTHEASTERN UNIVERSITY · PI Raymond G. Booth, Alexandros Makriyannis · 2022 to 2026
$1.3M
NIDA NIH HHS T32 DA055553NIDA NIH HHS T32DA055553NIDA NIH HHS U01 DA050243NIDA NIH HHS U01DA050243NIDA NIH HHS U01 DA055299NIDA NIH HHS U01DA55299
6 · The paper itself

Abstract

rationaleOpioid use during pregnancy can lead to negative infant health outcomes, including neonatal opioid withdrawal syndrome (NOWS). NOWS comprises gastrointestinal, autonomic nervous system, and neurological dysfunction that manifest during spontaneous withdrawal. Variability in NOWS severity necessitates a more individualized treatment approach. Ultrasonic vocalizations (USVs) in neonatal mice are emitted in isolation as a stress response and are increased during opioid withdrawal, thus modeling a negative affective state that can be utilized to test new treatments.

objectivesWe sought to identify the behavioral and USV profile, brainstem transcriptomic adaptations, and role of kappa opioid receptors in USVs during neonatal opioid withdrawal.

methodsWe employed a third trimester-approximate opioid exposure model, where neonatal inbred FVB/NJ pups were injected twice-daily with morphine (10mg/kg, s.c.) or saline (0.9%, 20 ul/g, s.c.) from postnatal day(P) 1 to P14. This protocol induces reduced weight gain, hypothermia, thermal hyperalgesia, and increased USVs during spontaneous morphine withdrawal.

resultsOn P14, there were increased USV emissions and altered USV syllables during withdrawal, including an increase in Complex 3 syllables in FVB/NJ females (but not males). Brainstem bulk mRNA sequencing revealed an upregulation of the kappa opioid receptor (Oprk1), which contributes to withdrawal-induced dysphoria. The kappa opioid receptor (KOR) antagonist, nor-BNI (30 mg/kg, s.c.), significantly reduced USVs in FVB/NJ females, but not males during spontaneous morphine withdrawal. Furthermore, the KOR agonist, U50,488h (0.625 mg/kg, s.c.), was sufficient to increase USVs on P10 (both sexes) and P14 (females only) in FVB/NJ mice.

conclusionsWe identified an elevated USV syllable, Complex 3, and a female-specific recruitment of the dynorphin/KOR system in increased USVs associated with neonatal opioid withdrawal severity.

Indexed as

Neonatal Abstinence SyndromeReceptors, Opioid, kappaSubstance Withdrawal SyndromeVocalization, AnimalAnalgesics, OpioidAnimalsAnimals, NewbornBrain StemDisease Models, AnimalFemaleMaleMiceMorphineNaltrexoneNarcotic AntagonistsPregnancyAnalgesics, OpioidMorphineNaltrexoneNarcotic AntagonistsReceptors, Opioid, kappaBrainstemEmotional-affective withdrawalKappa opioid receptorMorphineNeonatal opioid withdrawal syndromeRNA-seqSex differencesSpectrotemporal profileTranscriptomeUltrasonic vocalizations

Identifiers

PMID39348003
PMCPMC11775077

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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.