ArticleThe Journal of pharmacology and experimental therapeutics2022
Zhx2 Is a Candidate Gene Underlying Oxymorphone Metabolite Brain Concentration Associated with State-Dependent Oxycodone Reward.
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Article in The Journal of pharmacology and experimental therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9citing papers in PubMed
1.0field-weighted citation impact, top 28% of its field
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Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- Genetic Modulation of Oxycodone Self-Administration Trajectories: From Initiation to Escalating Burst Patterns.bioRxiv : the preprint server for biology · 2026Article
- Genetic modulation of oxycodone self-administration trajectories: from initiation to escalating burst patterns.Frontiers in behavioral neuroscience · 2026Article
- The acoustic properties, syllable structure, and syllable sequences of ultrasonic vocalizations (USVs) during neonatal opioid withdrawal in FVB/N mouse substrains.Addiction neuroscience · 2025Article
- Validation studies and multiomics analysis of Zhx2 as a candidate quantitative trait gene underlying brain oxycodone metabolite (oxymorphone) levels and behavior.The Journal of pharmacology and experimental therapeutics · 2025Article
- Atp1a2 and Kcnj9 Are Candidate Genes Underlying Sensitivity to Oxycodone-Induced Locomotor Activation and Withdrawal-Induced Anxiety-Like Behaviors in C57BL/6 Substrains.Genes, brain, and behavior · 2025Article
- Article
- Opioid trail: Tracking contributions to opioid use disorder from host genetics to the gut microbiome.Neuroscience and biobehavioral reviews · 2024Review
- Oxycodone: A Current Perspective on Its Pharmacology, Abuse, and Pharmacotherapeutic Developments.Pharmacological reviews · 2023Review
- Assessment of Binge-Like Eating of Unsweetened vs. Sweetened Chow Pellets in BALB/c Substrains.Frontiers in behavioral neuroscience · 2022Article
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Authors and funding
16 authors at 1 institution in 1 country.
Jacob A BeierlePh.D. Program in Biomolecular Pharmacology (J.A.B., S.I.G.), Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry (J.A.B., E.J.Y., W.B.L., J.L.S., A.A.S., K.D.S., A.L.W., C.D.B.), Department of Biology and Biochemistry, Center for Network Systems Biology (S.I.G., A.E.), and Graduate Program in Neuroscience (W.B.L), Boston University School of Medicine, Boston, Massachusetts; Transformative Training Program in Addiction Science (TTPAS) (J.A.B., W.B.L.) and Undergraduate Research Opportunity Program (J.L.S., K.D.S.), Boston University, Boston, Massachusetts; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (C.L.L., M.T.F.); Department of Pharmacology and Toxicity, Center for Human Toxicology, University of Utah, Salt Lake City, Utah (O.A., D.E.M., C.A.R.); and Department of Anesthesiology, Pain, and Preoperative Medicine Stanford University School of Medicine, Stanford, California (G.P.) camron@bu.edu.ORCID 0000-0001-6517-7614
Emily J YaoPh.D. Program in Biomolecular Pharmacology (J.A.B., S.I.G.), Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry (J.A.B., E.J.Y., W.B.L., J.L.S., A.A.S., K.D.S., A.L.W., C.D.B.), Department of Biology and Biochemistry, Center for Network Systems Biology (S.I.G., A.E.), and Graduate Program in Neuroscience (W.B.L), Boston University School of Medicine, Boston, Massachusetts; Transformative Training Program in Addiction Science (TTPAS) (J.A.B., W.B.L.) and Undergraduate Research Opportunity Program (J.L.S., K.D.S.), Boston University, Boston, Massachusetts; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (C.L.L., M.T.F.); Department of Pharmacology and Toxicity, Center for Human Toxicology, University of Utah, Salt Lake City, Utah (O.A., D.E.M., C.A.R.); and Department of Anesthesiology, Pain, and Preoperative Medicine Stanford University School of Medicine, Stanford, California (G.P.).
Stanley I GoldsteinPh.D. Program in Biomolecular Pharmacology (J.A.B., S.I.G.), Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry (J.A.B., E.J.Y., W.B.L., J.L.S., A.A.S., K.D.S., A.L.W., C.D.B.), Department of Biology and Biochemistry, Center for Network Systems Biology (S.I.G., A.E.), and Graduate Program in Neuroscience (W.B.L), Boston University School of Medicine, Boston, Massachusetts; Transformative Training Program in Addiction Science (TTPAS) (J.A.B., W.B.L.) and Undergraduate Research Opportunity Program (J.L.S., K.D.S.), Boston University, Boston, Massachusetts; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (C.L.L., M.T.F.); Department of Pharmacology and Toxicity, Center for Human Toxicology, University of Utah, Salt Lake City, Utah (O.A., D.E.M., C.A.R.); and Department of Anesthesiology, Pain, and Preoperative Medicine Stanford University School of Medicine, Stanford, California (G.P.).
William B LynchPh.D. Program in Biomolecular Pharmacology (J.A.B., S.I.G.), Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry (J.A.B., E.J.Y., W.B.L., J.L.S., A.A.S., K.D.S., A.L.W., C.D.B.), Department of Biology and Biochemistry, Center for Network Systems Biology (S.I.G., A.E.), and Graduate Program in Neuroscience (W.B.L), Boston University School of Medicine, Boston, Massachusetts; Transformative Training Program in Addiction Science (TTPAS) (J.A.B., W.B.L.) and Undergraduate Research Opportunity Program (J.L.S., K.D.S.), Boston University, Boston, Massachusetts; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (C.L.L., M.T.F.); Department of Pharmacology and Toxicity, Center for Human Toxicology, University of Utah, Salt Lake City, Utah (O.A., D.E.M., C.A.R.); and Department of Anesthesiology, Pain, and Preoperative Medicine Stanford University School of Medicine, Stanford, California (G.P.).
Julia L ScotellaroPh.D. Program in Biomolecular Pharmacology (J.A.B., S.I.G.), Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry (J.A.B., E.J.Y., W.B.L., J.L.S., A.A.S., K.D.S., A.L.W., C.D.B.), Department of Biology and Biochemistry, Center for Network Systems Biology (S.I.G., A.E.), and Graduate Program in Neuroscience (W.B.L), Boston University School of Medicine, Boston, Massachusetts; Transformative Training Program in Addiction Science (TTPAS) (J.A.B., W.B.L.) and Undergraduate Research Opportunity Program (J.L.S., K.D.S.), Boston University, Boston, Massachusetts; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (C.L.L., M.T.F.); Department of Pharmacology and Toxicity, Center for Human Toxicology, University of Utah, Salt Lake City, Utah (O.A., D.E.M., C.A.R.); and Department of Anesthesiology, Pain, and Preoperative Medicine Stanford University School of Medicine, Stanford, California (G.P.).
Anyaa A ShahPh.D. Program in Biomolecular Pharmacology (J.A.B., S.I.G.), Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry (J.A.B., E.J.Y., W.B.L., J.L.S., A.A.S., K.D.S., A.L.W., C.D.B.), Department of Biology and Biochemistry, Center for Network Systems Biology (S.I.G., A.E.), and Graduate Program in Neuroscience (W.B.L), Boston University School of Medicine, Boston, Massachusetts; Transformative Training Program in Addiction Science (TTPAS) (J.A.B., W.B.L.) and Undergraduate Research Opportunity Program (J.L.S., K.D.S.), Boston University, Boston, Massachusetts; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (C.L.L., M.T.F.); Department of Pharmacology and Toxicity, Center for Human Toxicology, University of Utah, Salt Lake City, Utah (O.A., D.E.M., C.A.R.); and Department of Anesthesiology, Pain, and Preoperative Medicine Stanford University School of Medicine, Stanford, California (G.P.).
Katherine D SenaPh.D. Program in Biomolecular Pharmacology (J.A.B., S.I.G.), Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry (J.A.B., E.J.Y., W.B.L., J.L.S., A.A.S., K.D.S., A.L.W., C.D.B.), Department of Biology and Biochemistry, Center for Network Systems Biology (S.I.G., A.E.), and Graduate Program in Neuroscience (W.B.L), Boston University School of Medicine, Boston, Massachusetts; Transformative Training Program in Addiction Science (TTPAS) (J.A.B., W.B.L.) and Undergraduate Research Opportunity Program (J.L.S., K.D.S.), Boston University, Boston, Massachusetts; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (C.L.L., M.T.F.); Department of Pharmacology and Toxicity, Center for Human Toxicology, University of Utah, Salt Lake City, Utah (O.A., D.E.M., C.A.R.); and Department of Anesthesiology, Pain, and Preoperative Medicine Stanford University School of Medicine, Stanford, California (G.P.).
Alyssa L WongPh.D. Program in Biomolecular Pharmacology (J.A.B., S.I.G.), Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry (J.A.B., E.J.Y., W.B.L., J.L.S., A.A.S., K.D.S., A.L.W., C.D.B.), Department of Biology and Biochemistry, Center for Network Systems Biology (S.I.G., A.E.), and Graduate Program in Neuroscience (W.B.L), Boston University School of Medicine, Boston, Massachusetts; Transformative Training Program in Addiction Science (TTPAS) (J.A.B., W.B.L.) and Undergraduate Research Opportunity Program (J.L.S., K.D.S.), Boston University, Boston, Massachusetts; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (C.L.L., M.T.F.); Department of Pharmacology and Toxicity, Center for Human Toxicology, University of Utah, Salt Lake City, Utah (O.A., D.E.M., C.A.R.); and Department of Anesthesiology, Pain, and Preoperative Medicine Stanford University School of Medicine, Stanford, California (G.P.).
Colton L LinnertzPh.D. Program in Biomolecular Pharmacology (J.A.B., S.I.G.), Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry (J.A.B., E.J.Y., W.B.L., J.L.S., A.A.S., K.D.S., A.L.W., C.D.B.), Department of Biology and Biochemistry, Center for Network Systems Biology (S.I.G., A.E.), and Graduate Program in Neuroscience (W.B.L), Boston University School of Medicine, Boston, Massachusetts; Transformative Training Program in Addiction Science (TTPAS) (J.A.B., W.B.L.) and Undergraduate Research Opportunity Program (J.L.S., K.D.S.), Boston University, Boston, Massachusetts; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (C.L.L., M.T.F.); Department of Pharmacology and Toxicity, Center for Human Toxicology, University of Utah, Salt Lake City, Utah (O.A., D.E.M., C.A.R.); and Department of Anesthesiology, Pain, and Preoperative Medicine Stanford University School of Medicine, Stanford, California (G.P.).
Olga AverinPh.D. Program in Biomolecular Pharmacology (J.A.B., S.I.G.), Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry (J.A.B., E.J.Y., W.B.L., J.L.S., A.A.S., K.D.S., A.L.W., C.D.B.), Department of Biology and Biochemistry, Center for Network Systems Biology (S.I.G., A.E.), and Graduate Program in Neuroscience (W.B.L), Boston University School of Medicine, Boston, Massachusetts; Transformative Training Program in Addiction Science (TTPAS) (J.A.B., W.B.L.) and Undergraduate Research Opportunity Program (J.L.S., K.D.S.), Boston University, Boston, Massachusetts; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (C.L.L., M.T.F.); Department of Pharmacology and Toxicity, Center for Human Toxicology, University of Utah, Salt Lake City, Utah (O.A., D.E.M., C.A.R.); and Department of Anesthesiology, Pain, and Preoperative Medicine Stanford University School of Medicine, Stanford, California (G.P.).
David E MoodyPh.D. Program in Biomolecular Pharmacology (J.A.B., S.I.G.), Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry (J.A.B., E.J.Y., W.B.L., J.L.S., A.A.S., K.D.S., A.L.W., C.D.B.), Department of Biology and Biochemistry, Center for Network Systems Biology (S.I.G., A.E.), and Graduate Program in Neuroscience (W.B.L), Boston University School of Medicine, Boston, Massachusetts; Transformative Training Program in Addiction Science (TTPAS) (J.A.B., W.B.L.) and Undergraduate Research Opportunity Program (J.L.S., K.D.S.), Boston University, Boston, Massachusetts; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (C.L.L., M.T.F.); Department of Pharmacology and Toxicity, Center for Human Toxicology, University of Utah, Salt Lake City, Utah (O.A., D.E.M., C.A.R.); and Department of Anesthesiology, Pain, and Preoperative Medicine Stanford University School of Medicine, Stanford, California (G.P.).
Christopher A ReillyPh.D. Program in Biomolecular Pharmacology (J.A.B., S.I.G.), Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry (J.A.B., E.J.Y., W.B.L., J.L.S., A.A.S., K.D.S., A.L.W., C.D.B.), Department of Biology and Biochemistry, Center for Network Systems Biology (S.I.G., A.E.), and Graduate Program in Neuroscience (W.B.L), Boston University School of Medicine, Boston, Massachusetts; Transformative Training Program in Addiction Science (TTPAS) (J.A.B., W.B.L.) and Undergraduate Research Opportunity Program (J.L.S., K.D.S.), Boston University, Boston, Massachusetts; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (C.L.L., M.T.F.); Department of Pharmacology and Toxicity, Center for Human Toxicology, University of Utah, Salt Lake City, Utah (O.A., D.E.M., C.A.R.); and Department of Anesthesiology, Pain, and Preoperative Medicine Stanford University School of Medicine, Stanford, California (G.P.).ORCID 0000-0002-5006-1982
Gary PeltzPh.D. Program in Biomolecular Pharmacology (J.A.B., S.I.G.), Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry (J.A.B., E.J.Y., W.B.L., J.L.S., A.A.S., K.D.S., A.L.W., C.D.B.), Department of Biology and Biochemistry, Center for Network Systems Biology (S.I.G., A.E.), and Graduate Program in Neuroscience (W.B.L), Boston University School of Medicine, Boston, Massachusetts; Transformative Training Program in Addiction Science (TTPAS) (J.A.B., W.B.L.) and Undergraduate Research Opportunity Program (J.L.S., K.D.S.), Boston University, Boston, Massachusetts; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (C.L.L., M.T.F.); Department of Pharmacology and Toxicity, Center for Human Toxicology, University of Utah, Salt Lake City, Utah (O.A., D.E.M., C.A.R.); and Department of Anesthesiology, Pain, and Preoperative Medicine Stanford University School of Medicine, Stanford, California (G.P.).
Andrew EmiliPh.D. Program in Biomolecular Pharmacology (J.A.B., S.I.G.), Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry (J.A.B., E.J.Y., W.B.L., J.L.S., A.A.S., K.D.S., A.L.W., C.D.B.), Department of Biology and Biochemistry, Center for Network Systems Biology (S.I.G., A.E.), and Graduate Program in Neuroscience (W.B.L), Boston University School of Medicine, Boston, Massachusetts; Transformative Training Program in Addiction Science (TTPAS) (J.A.B., W.B.L.) and Undergraduate Research Opportunity Program (J.L.S., K.D.S.), Boston University, Boston, Massachusetts; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (C.L.L., M.T.F.); Department of Pharmacology and Toxicity, Center for Human Toxicology, University of Utah, Salt Lake City, Utah (O.A., D.E.M., C.A.R.); and Department of Anesthesiology, Pain, and Preoperative Medicine Stanford University School of Medicine, Stanford, California (G.P.).
Martin T FerrisPh.D. Program in Biomolecular Pharmacology (J.A.B., S.I.G.), Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry (J.A.B., E.J.Y., W.B.L., J.L.S., A.A.S., K.D.S., A.L.W., C.D.B.), Department of Biology and Biochemistry, Center for Network Systems Biology (S.I.G., A.E.), and Graduate Program in Neuroscience (W.B.L), Boston University School of Medicine, Boston, Massachusetts; Transformative Training Program in Addiction Science (TTPAS) (J.A.B., W.B.L.) and Undergraduate Research Opportunity Program (J.L.S., K.D.S.), Boston University, Boston, Massachusetts; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (C.L.L., M.T.F.); Department of Pharmacology and Toxicity, Center for Human Toxicology, University of Utah, Salt Lake City, Utah (O.A., D.E.M., C.A.R.); and Department of Anesthesiology, Pain, and Preoperative Medicine Stanford University School of Medicine, Stanford, California (G.P.).
Camron D BryantPh.D. Program in Biomolecular Pharmacology (J.A.B., S.I.G.), Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Psychiatry (J.A.B., E.J.Y., W.B.L., J.L.S., A.A.S., K.D.S., A.L.W., C.D.B.), Department of Biology and Biochemistry, Center for Network Systems Biology (S.I.G., A.E.), and Graduate Program in Neuroscience (W.B.L), Boston University School of Medicine, Boston, Massachusetts; Transformative Training Program in Addiction Science (TTPAS) (J.A.B., W.B.L.) and Undergraduate Research Opportunity Program (J.L.S., K.D.S.), Boston University, Boston, Massachusetts; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (C.L.L., M.T.F.); Department of Pharmacology and Toxicity, Center for Human Toxicology, University of Utah, Salt Lake City, Utah (O.A., D.E.M., C.A.R.); and Department of Anesthesiology, Pain, and Preoperative Medicine Stanford University School of Medicine, Stanford, California (G.P.).
Boston University · US
Funding
Unlocking Zika Virus Immune Control and Pathogenesis with the Collaborative CrossU19AI100625 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MCWEENEY, SHANNON K. · 2012 to 2021
$36.6MSystems Genetics of TuberculosisP01AI132130 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BEHAR, SAMUEL M · 2017 to 2021
$11.2MTRAINING IN BIOMOLECULAR PHARMACOLOGYT32GM008541 · NIGMS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI FARB, DAVID H · 1997 to 2022
$5.2MA 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
$3.3MBridging genetic variation with behavior: Molecular and functional mechanisms of quantitative trait gene regulation of the stimulant and addictive properties of methamphetamine in miceR01DA039168 · NIDA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BRYANT, CAMRON D · 2015 to 2019
$3.0MThe role of Zhx2 in CYP2D regulation, oxycodone metabolism, and opioid addiction model behaviors.F31DA056217 · NIDA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI LYNCH, WILLIAM · 2023 to 2024
$97kNIAID NIH HHS P01 AI132130NIAID NIH HHS U19 AI100625NIDA NIH HHS F31 DA056217NIDA NIH HHS R01 DA039168NIDA NIH HHS U01 DA050243NIGMS NIH HHS T32 GM008541
Abstract
Understanding the pharmacogenomics of opioid metabolism and behavior is vital to therapeutic success, as mutations can dramatically alter therapeutic efficacy and addiction liability. We found robust, sex-dependent BALB/c substrain differences in oxycodone behaviors and whole brain concentration of oxycodone metabolites. BALB/cJ females showed robust state-dependent oxycodone reward learning as measured via conditioned place preference when compared with the closely related BALB/cByJ substrain. Accordingly, BALB/cJ females also showed a robust increase in brain concentration of the inactive metabolite noroxycodone and the active metabolite oxymorphone compared with BALB/cByJ mice. Oxymorphone is a highly potent, full agonist at the mu opioid receptor that could enhance drug-induced interoception and state-dependent oxycodone reward learning. Quantitative trait locus (QTL) mapping in a BALB/c F2 reduced complexity cross revealed one major QTL on chromosome 15 underlying brain oxymorphone concentration that explained 32% of the female variance. BALB/cJ and BALB/cByJ differ by fewer than 10,000 variants, which can greatly facilitate candidate gene/variant identification. Hippocampal and striatal cis-expression QTL (eQTL) and exon-level eQTL analysis identified
Indexed as
BrainHomeodomain ProteinsOxycodoneOxymorphoneAnalgesics, OpioidAnimalsFemaleMaleMiceMice, Inbred BALB CRewardAnalgesics, OpioidHomeodomain ProteinsOxycodoneOxymorphoneZhx2 protein, mouse
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