Evidence map›Paper›PMID 35064236›Full record

ArticleMolecular psychiatry2022

Involvement of the ghrelin system in the maintenance of oxycodone self-administration: converging evidence from endocrine, pharmacologic and transgenic approaches.

Zhi-Bing You, Eliot L Gardner, Ewa Galaj, Allamar R Moore, Tristram Buck, Chloe J Jordan, Bree A Humburg, Guo-Hua Bi, Zheng-Xiong Xi, Lorenzo Leggio

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

Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 22% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Review
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  5. Review
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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

10 authors at 1 institution in 1 country.

Zhi-Bing YouMolecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
Eliot L GardnerMolecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
Ewa GalajMolecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
Allamar R MooreMolecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
Tristram BuckMolecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
Chloe J JordanMolecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-1843-227X
Bree A HumburgMolecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
Guo-Hua BiMolecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
Zheng-Xiong XiMolecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
Lorenzo LeggioClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, Baltimore, MD, USA. lorenzo.leggio@nih.gov.ORCID http://orcid.org/0000-0001-7284-8754
National Institute on Drug Abuse · US

Funding

Clinical Psychoneuroendocrinology and Neuropsychopharmacology (CPN)ZIADA000635 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI LEGGIO, LORENZO · 2020 to 2025
$15.2M
Basic brain mechanisms underlying drug addiction, craving, and relapseZIADA000478 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI GARDNER, ELIOT · 2009 to 2023
$7.9M
Intramural NIH HHS ZIA DA000635
6 · The paper itself

Abstract

Ghrelin, an orexigenic hormone, has emerged as a critical biological substrate implicated in drug reward. However, the response of the ghrelin system to opioid-motivated behaviors and the role of ghrelin in oxycodone self-administration remain to be studied. Here, we investigated the reciprocal interactions between the endogenous ghrelin system and oxycodone self-administration behaviors in rats and the role of the ghrelin system in brain stimulation reward (BSR) driven by optogenetic stimulation of midbrain reward circuits in mice. Oxycodone self-administration significantly elevated plasma ghrelin, des-acyl ghrelin and growth hormone and showed no effect on plasma LEAP2, a newly identified endogenous ghrelin receptor (GHS-R1a) antagonist. Oxycodone self-administration produced significant decreases in plasma gastric inhibitory polypeptide and insulin. Acquisition of oxycodone self-administration significantly upregulated GHS-R1a mRNA levels in dopamine neurons in the ventral tegmental area (VTA), a brain region critical in drug reward. Pretreatment with JMV2959, a selective GHS-R1a antagonist, dose-dependently reduced oxycodone self-administration and decreased the breakpoint for oxycodone under a progressive ratio reinforcement in Long-Evans rats. The inhibitory effects of JMV2959 on oxycodone self-administration is selectively mediated by GHS-R1a as JMV2959 showed a similar effect in Wistar wildtype but not in GHS-R knockout rats. JMV2959 pretreatment significantly inhibited BSR driven by selective stimulation of VTA dopamine neurons, but not by stimulation of striatal GABA neurons projecting to the VTA in mice. These findings suggest that elevation of ghrelin signaling by oxycodone or oxycodone-associated stimuli is a causal process by which oxycodone motivates oxycodone drug-taking and targeting the ghrelin system may be a viable treatment approach for opioid use disorders.

Indexed as

GhrelinReceptors, GhrelinAnimalsAnimals, Genetically ModifiedMiceOxycodoneRatsRats, Long-EvansRats, WistarGhrelinOxycodoneReceptors, Ghrelin

Identifiers

PMID35064236
PMCPMC9133122
OpenAlexW4207085235

What OpenQuestion holds

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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.