Evidence map›Paper›PMID 39096973›Full record

ArticlePharmacology, biochemistry, and behavior2024

Kappa-opioid receptor antagonism in the nucleus accumbens shell distinguishes escalated alcohol consumption and negative affective-like behavior from physiological withdrawal in alcohol-dependence.

Gaetan Lepreux, Angela M Henricks, Gengze Wei, Bok Soon Go, Chloe M Erikson, Rachel M Abella, Amy Pham, Brendan M Walker

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In one paragraph

Article in Pharmacology, biochemistry, and behavior, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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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

4 citing papers in PubMed.

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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

8 authors.

Gaetan LepreuxDepartment of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Angela M HenricksDepartment of Psychology, Washington State University, Pullman, WA, USA.
Gengze WeiDepartment of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, FL, USA; Department of Psychology, Washington State University, Pullman, WA, USA.
Bok Soon GoDepartment of Life Sciences, Korea University, Seoul, South Korea.
Chloe M EriksonDepartment of Psychology, Washington State University, Pullman, WA, USA.
Rachel M AbellaDepartment of Psychology, Washington State University, Pullman, WA, USA.
Amy PhamDepartment of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Brendan M WalkerDepartment of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, FL, USA; Department of Psychology, Washington State University, Pullman, WA, USA; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA; USF Neuroscience Institute, USF Health, University of South Florida, Tampa, FL, USA. Electronic address: bwalker@usf.edu.

Funding

The Role of Kappa-Opioid Receptors in Alcohol Use DisordersR01AA020394 · NIAAA · WASHINGTON STATE UNIVERSITY · PI WALKER, BRENDAN M · 2011 to 2022
$3.8M
Oprk1-regulated neurocircuitry and phenotypes of alcohol use disorderR01AA031171 · NIAAA · UNIVERSITY OF SOUTH FLORIDA · PI Brendan M Walker · 2023 to 2026
$2.2M
NIAAA NIH HHS R01 AA020394NIAAA NIH HHS R01 AA031171
6 · The paper itself

Abstract

Alcohol use disorder (AUD) is a chronic relapsing disease that is deleterious at individual, familial, and societal levels. Although AUD is one of the highest preventable causes of death in the USA, therapies for the treatment of AUD are not sufficient given the heterogeneity of the disorder and the limited number of approved medications. To provide better pharmacological strategies, it is important to understand the neurological underpinnings of AUD. Evidence implicates the endogenous dynorphin (DYN)/κ-opioid receptor (KOR) system recruitment in dysphoric and negative emotional states in AUD to promote maladaptive behavioral regulation. The nucleus accumbens shell (AcbSh), mediating motivational and emotional processes that is a component of the mesolimbic dopamine system and the extended amygdala, is an important site related to alcohol's reinforcing actions (both positive and negative) and neuroadaptations in the AcbSh DYN/KOR system have been documented to induce maladaptive symptoms in AUD. We have previously shown that in other nodes of the extended amygdala, site-specific KOR antagonism can distinguish different symptoms of alcohol dependence and withdrawal. In the current study, we examined the role of the KOR signaling in the AcbSh of male Wistar rats in operant alcohol self-administration, measures of negative affective-like behavior, and physiological symptoms during acute alcohol withdrawal in alcohol-dependence. To induce alcohol dependence, rats were exposed to chronic intermittent ethanol vapor for 14 h/day for three months, during which stable escalation of alcohol self-administration was achieved and pharmacological AcbSh KOR antagonism ensued. The results showed that AcbSh KOR antagonism significantly reduced escalated alcohol intake and negative affective-like states but did not alter somatic symptoms of withdrawal. Understanding the relative contribution of these different drivers is important to understand and inform therapeutic efficacy approaches in alcohol dependence and further emphasis the importance of the KOR/DYN system as a target for AUD therapeutics.

Indexed as

Alcohol DrinkingAlcoholismNucleus AccumbensReceptors, Opioid, kappaSubstance Withdrawal SyndromeAnimalsBehavior, AnimalEthanolMaleNarcotic AntagonistsPyrrolidinesRatsSelf AdministrationEthanolNarcotic AntagonistsPyrrolidinesReceptors, Opioid, kappaAlcoholAlcohol use disorderDynorphinDysregulationElevated plus mazeEthanolExtended amygdalaForced swim testKappa opioid receptorMaladaptive behavioral regulationNucleus accumbensPharmacotherapyPhysiological withdrawalSelf-administrationSomatic withdrawalUltrasonic vocalization

Identifiers

PMID39096973
PMCPMC12893421

What OpenQuestion holds

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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.