Evidence map›Paper›PMID 26992699›Full record

ArticleAlcohol (Fayetteville, N.Y.)2016

Species differences in the effects of the κ-opioid receptor antagonist zyklophin.

Sunil Sirohi, Jane V Aldrich, Brendan M Walker

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alcohol (Fayetteville, N.Y.), 2016. 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
0.8field-weighted citation impact, top 27% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Enhancement of a Heroin Vaccine through Hapten Deuteration.Journal of the American Chemical Society · 2020
    Article
  2. Review
  3. Article
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

3 authors at 2 institutions in 1 country.

Sunil SirohiLaboratory of Alcoholism and Addictions Neuroscience, Department of Psychology, Washington State University, Pullman, WA, USA; Department of Integrative Physiology & Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
Jane V AldrichDepartment of Medicinal Chemistry, University of Florida, Gainesville, FL, USA.
Brendan M WalkerLaboratory of Alcoholism and Addictions Neuroscience, Department of Psychology, Washington State University, Pullman, WA, USA; Department of Integrative Physiology & Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, WA, USA; Graduate Program in Neuroscience, Washington State University, Pullman, WA, USA; Translational Addiction Research Center, Washington State University, Pullman, WA, USA. Electronic address: b_walker@wsu.edu.
Washington State University · USUniversity of Florida · US

Funding

Peptidic Kappa Opioid Receptor Ligands as Potential Treatments for Drug AddictionR01DA023924 · NIDA · UNIVERSITY OF KANSAS LAWRENCE · PI ALDRICH, JANE V · 2007 to 2018
$5.3M
The Role of Kappa-Opioid Receptors in Alcohol Use DisordersR01AA020394 · NIAAA · WASHINGTON STATE UNIVERSITY · PI WALKER, BRENDAN M · 2011 to 2022
$3.8M
NIAAA NIH HHS R01 AA020394NIAAA NIH HHS R01AA020394NIDA NIH HHS R01 DA023924NIDA NIH HHS R01DA023924-07
6 · The paper itself

Abstract

We have shown that dysregulation of the dynorphin/kappa-opioid receptor (DYN/KOR) system contributes to escalated alcohol self-administration in alcohol dependence and that KOR antagonists with extended durations of action selectively reduce escalated alcohol consumption in alcohol-dependent animals. As KOR antagonism has gained widespread attention as a potential therapeutic target to treat alcoholism and multiple neuropsychiatric disorders, we tested the effect of zyklophin (a short-acting KOR antagonist) on escalated alcohol self-administration in rats made alcohol-dependent using intermittent alcohol vapor exposure. Following dependence induction, zyklophin was infused centrally prior to alcohol self-administration sessions and locomotor activity tests during acute withdrawal. Zyklophin did not impact alcohol self-administration or locomotor activity in either exposure condition. To investigate the neurobiological basis of this atypical effect for a KOR antagonist, we utilized a κ-, μ-, and δ-opioid receptor agonist-stimulated GTPyS coupling assay to examine the opioid receptor specificity of zyklophin in the rat brain and mouse brain. In rats, zyklophin did not affect U50488-, DAMGO-, or DADLE-stimulated GTPyS coupling, whereas the prototypical KOR antagonist nor-binaltorphimine (norBNI) attenuated U50488-induced stimulation in the rat brain tissue at concentrations that did not impact μ- and δ-receptor function. To reconcile the discrepancy between the present rat data and published mouse data, comparable GTPyS assays were conducted using mouse brain tissue; zyklophin effects were consistent with KOR antagonism in mice. Moreover, at higher concentrations, zyklophin exhibited agonist properties in rat and mouse brains. These results identify species differences in zyklophin efficacy that, given the rising interest in the development of short-duration KOR antagonists, should provide valuable information for therapeutic development efforts.

Indexed as

AnimalsDose-Response Relationship, DrugDynorphinsEthanolMaleMiceMice, Inbred C57BLNarcotic AntagonistsPeptide FragmentsRatsRats, WistarReceptors, Opioid, kappaSelf AdministrationSpecies SpecificitySubstance Withdrawal Syndromedynorphin A-(1-11)-NH2, Nalpha-benzylTyr(1)-cyclo(Asp(5)-Dap(8))-DynorphinsEthanolNarcotic AntagonistsPeptide FragmentsReceptors, Opioid, kappaAlcohol dependence and withdrawalAlcohol self-administrationGTPyS couplingKappa-opioid receptorZyklophin

Identifiers

PMID26992699
PMCPMC4879959
OpenAlexW2263500275

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.