Evidence map›Paper›PMID 31028107›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2019

In Utero Exposure to Norbuprenorphine, a Major Metabolite of Buprenorphine, Induces Fetal Opioid Dependence and Leads to Neonatal Opioid Withdrawal Syndrome.

Bryce A Griffin, Caitlin O Caperton, Lauren N Russell, Christian V Cabanlong, Catheryn D Wilson, Kyle R Urquhart, Bradford S Martins, Marcelle Dina Zita, Amy L Patton, Alexander W Alund and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
4.4field-weighted citation impact, top 6% of its field
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

13 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
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  3. Limited bedding and nesting increases ethanol drinking in female rats.Pharmacology, biochemistry, and behavior · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Bryce A GriffinDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas (B.A.G.); Departments of Pharmacology and Toxicology (C.O.C., L.N.R., C.V.C., C.D.W., K.R.U., S.M.O., W.E.F., J.H.M., L.K.B.), Psychiatry (B.S.M.), and Microbiology and Immunology (M.D.Z.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and PinPoint Testing, LLC, Little Rock, Arkansas (A.L.P., A.W.A., J.H.M.).
Caitlin O CapertonDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas (B.A.G.); Departments of Pharmacology and Toxicology (C.O.C., L.N.R., C.V.C., C.D.W., K.R.U., S.M.O., W.E.F., J.H.M., L.K.B.), Psychiatry (B.S.M.), and Microbiology and Immunology (M.D.Z.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and PinPoint Testing, LLC, Little Rock, Arkansas (A.L.P., A.W.A., J.H.M.).
Lauren N RussellDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas (B.A.G.); Departments of Pharmacology and Toxicology (C.O.C., L.N.R., C.V.C., C.D.W., K.R.U., S.M.O., W.E.F., J.H.M., L.K.B.), Psychiatry (B.S.M.), and Microbiology and Immunology (M.D.Z.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and PinPoint Testing, LLC, Little Rock, Arkansas (A.L.P., A.W.A., J.H.M.).
Christian V CabanlongDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas (B.A.G.); Departments of Pharmacology and Toxicology (C.O.C., L.N.R., C.V.C., C.D.W., K.R.U., S.M.O., W.E.F., J.H.M., L.K.B.), Psychiatry (B.S.M.), and Microbiology and Immunology (M.D.Z.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and PinPoint Testing, LLC, Little Rock, Arkansas (A.L.P., A.W.A., J.H.M.).
Catheryn D WilsonDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas (B.A.G.); Departments of Pharmacology and Toxicology (C.O.C., L.N.R., C.V.C., C.D.W., K.R.U., S.M.O., W.E.F., J.H.M., L.K.B.), Psychiatry (B.S.M.), and Microbiology and Immunology (M.D.Z.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and PinPoint Testing, LLC, Little Rock, Arkansas (A.L.P., A.W.A., J.H.M.).
Kyle R UrquhartDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas (B.A.G.); Departments of Pharmacology and Toxicology (C.O.C., L.N.R., C.V.C., C.D.W., K.R.U., S.M.O., W.E.F., J.H.M., L.K.B.), Psychiatry (B.S.M.), and Microbiology and Immunology (M.D.Z.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and PinPoint Testing, LLC, Little Rock, Arkansas (A.L.P., A.W.A., J.H.M.).
Bradford S MartinsDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas (B.A.G.); Departments of Pharmacology and Toxicology (C.O.C., L.N.R., C.V.C., C.D.W., K.R.U., S.M.O., W.E.F., J.H.M., L.K.B.), Psychiatry (B.S.M.), and Microbiology and Immunology (M.D.Z.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and PinPoint Testing, LLC, Little Rock, Arkansas (A.L.P., A.W.A., J.H.M.).
Marcelle Dina ZitaDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas (B.A.G.); Departments of Pharmacology and Toxicology (C.O.C., L.N.R., C.V.C., C.D.W., K.R.U., S.M.O., W.E.F., J.H.M., L.K.B.), Psychiatry (B.S.M.), and Microbiology and Immunology (M.D.Z.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and PinPoint Testing, LLC, Little Rock, Arkansas (A.L.P., A.W.A., J.H.M.).
Amy L PattonDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas (B.A.G.); Departments of Pharmacology and Toxicology (C.O.C., L.N.R., C.V.C., C.D.W., K.R.U., S.M.O., W.E.F., J.H.M., L.K.B.), Psychiatry (B.S.M.), and Microbiology and Immunology (M.D.Z.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and PinPoint Testing, LLC, Little Rock, Arkansas (A.L.P., A.W.A., J.H.M.).
Alexander W AlundDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas (B.A.G.); Departments of Pharmacology and Toxicology (C.O.C., L.N.R., C.V.C., C.D.W., K.R.U., S.M.O., W.E.F., J.H.M., L.K.B.), Psychiatry (B.S.M.), and Microbiology and Immunology (M.D.Z.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and PinPoint Testing, LLC, Little Rock, Arkansas (A.L.P., A.W.A., J.H.M.).
S Michael OwensDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas (B.A.G.); Departments of Pharmacology and Toxicology (C.O.C., L.N.R., C.V.C., C.D.W., K.R.U., S.M.O., W.E.F., J.H.M., L.K.B.), Psychiatry (B.S.M.), and Microbiology and Immunology (M.D.Z.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and PinPoint Testing, LLC, Little Rock, Arkansas (A.L.P., A.W.A., J.H.M.).
William E FantegrossiDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas (B.A.G.); Departments of Pharmacology and Toxicology (C.O.C., L.N.R., C.V.C., C.D.W., K.R.U., S.M.O., W.E.F., J.H.M., L.K.B.), Psychiatry (B.S.M.), and Microbiology and Immunology (M.D.Z.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and PinPoint Testing, LLC, Little Rock, Arkansas (A.L.P., A.W.A., J.H.M.).
Jeffery H MoranDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas (B.A.G.); Departments of Pharmacology and Toxicology (C.O.C., L.N.R., C.V.C., C.D.W., K.R.U., S.M.O., W.E.F., J.H.M., L.K.B.), Psychiatry (B.S.M.), and Microbiology and Immunology (M.D.Z.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and PinPoint Testing, LLC, Little Rock, Arkansas (A.L.P., A.W.A., J.H.M.).
Lisa K BrentsDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas (B.A.G.); Departments of Pharmacology and Toxicology (C.O.C., L.N.R., C.V.C., C.D.W., K.R.U., S.M.O., W.E.F., J.H.M., L.K.B.), Psychiatry (B.S.M.), and Microbiology and Immunology (M.D.Z.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; and PinPoint Testing, LLC, Little Rock, Arkansas (A.L.P., A.W.A., J.H.M.) LBRENTS@uams.edu.
University of Arkansas at Fayetteville · USUniversity of Arkansas for Medical Sciences · US

Funding

Zosuquidar trihydrochloride for acute myeloid leukemia &refractory anemiaM01RR000080 · NCRR · UNIVERSITY HOSPITALS OF CLEVELAND · PI DEARBORN, DORR GELLATLY · 1985 to 2007
$22.2M
Expanding Translational Research in ArkansasUL1TR003107 · NCATS · UNIV OF ARKANSAS FOR MED SCIS · PI JAMES, LAURA P · 2019 to 2023
$21.6M
Translational Training in AddictionT32DA022981 · NIDA · UNIV OF ARKANSAS FOR MED SCIS · PI Melissa Jean Zielinski · 2009 to 2026
$6.1M
The University of Arkansas for Medical Sciences Initiative for Maximizing Student Development ProgramR25GM083247 · NIGMS · UNIV OF ARKANSAS FOR MED SCIS · PI MCGEHEE, ROBERT E, THOMAS, BILLY R · 2009 to 2023
$5.4M
Expanding Translational Research in ArkansasU54TR001629 · NCATS · UNIV OF ARKANSAS FOR MED SCIS · PI JAMES, LAURA P · 2017 to 2017
$3.5M
Synthetic Cannabinoid Toxicity: Role of BiotransformationR01DA039143 · NIDA · UNIV OF ARKANSAS FOR MED SCIS · PI PRATHER, PAUL L · 2016 to 2020
$2.9M
Arkansas Center for Clinical Translational ResearchKL2TR000063 · NCATS · UNIV OF ARKANSAS FOR MED SCIS · PI BECK, CORNELIA MARIE, JAMES, LAURA P · 2012 to 2014
$459k
Multi-Level Modeling of Addiction ComorbidityF30DA043928 · NIDA · UNIV OF ARKANSAS FOR MED SCIS · PI MARTINS, BRADFORD · 2018 to 2020
$101k
NCATS NIH HHS KL2 TR000063NCATS NIH HHS U54 TR001629NCATS NIH HHS UL1 TR003107NCRR NIH HHS M01 RR000080NIDA NIH HHS F30 DA043928NIDA NIH HHS R01 DA039143NIDA NIH HHS T32 DA022981NIGMS NIH HHS R25 GM083247
6 · The paper itself

Abstract

Buprenorphine is the preferred treatment of opioid use disorder during pregnancy but can cause fetal opioid dependence and neonatal opioid withdrawal syndrome (NOWS). Notably, withdrawal severity is independent of maternal buprenorphine dose, suggesting that interindividual variance in pharmacokinetics may influence risk and severity of NOWS. Using a rat model of NOWS, we tested the hypothesis that clinically relevant doses of the active metabolite norbuprenorphine (NorBUP) can induce in utero opioid dependence, manifested as naltrexone-precipitated withdrawal signs in the neonate. Pregnant Long-Evans rats were implanted with 14-day osmotic minipumps containing vehicle, morphine (positive control), or NorBUP (0.3-10 mg/kg per day) on gestation day 9. By 12 hours post-delivery, an intraperitoneal injection of the opioid antagonist naltrexone (1 or 10 mg/kg) or saline was administered to pups. Precipitated withdrawal signs were graded by raters blinded to treatment conditions. In a separate group, NorBUP concentrations in maternal and fetal blood and brain on gestation day 20 were determined by liquid chromatography-tandem mass spectrometry. Steady-state maternal blood concentrations of NorBUP in dams infused with 1 or 3 mg/kg per day were comparable to values reported in pregnant humans treated with buprenorphine (1.0 and 9.6 ng/ml, respectively), suggesting a clinically relevant dosing regimen. At these doses, NorBUP increased withdrawal severity in the neonate as shown by an evaluation of 10 withdrawal indicators. These findings support the possibility that NorBUP contributes to fetal opioid dependence and NOWS following maternal buprenorphine treatment during pregnancy.

Indexed as

AnimalsAnimals, NewbornBuprenorphineFemaleFetusOpioid-Related DisordersPregnancyPrenatal Exposure Delayed EffectsRatsRiskSubstance Withdrawal SyndromeBuprenorphinenorbuprenorphine

Identifiers

PMID31028107
PMCPMC6538887
OpenAlexW2940752810

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.