Evidence map›Paper›PMID 40712753›Full record

ArticleNeuropharmacology2025

Sex-dependent role of Neuropeptide-S on anxiety, fear conditioning, and alcohol seeking in alcohol preferring rats.

Min Li, Sara De Carlo, Laura Soverchia, Scott P Runyon, Stewart Clark, Marisa Roberto, Carolina L Haass-Koffler, Roberto Ciccocioppo, Douglas J Sheffler, Nazzareno Cannella

Abstract read
In one paragraph

Article in Neuropharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–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

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, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Neuropeptidergic systems in psychiatric disorders.Frontiers in endocrinology · 2025
    Review
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.

Min LiSchool of Pharmacy, Center for Neuroscience, Pharmacology Unit, University of Camerino, Italy.
Sara De CarloSchool of Pharmacy, Center for Neuroscience, Pharmacology Unit, University of Camerino, Italy.
Laura SoverchiaSchool of Pharmacy, Center for Neuroscience, Pharmacology Unit, University of Camerino, Italy.
Scott P RunyonResearch Triangle Institute, Center for Drug Discovery, Research Triangle Park, NC, 27709, USA.
Stewart ClarkDepartment of Pharmacology and Toxicology, State University of New York at Buffalo, Buffalo, NY, USA.
Marisa RobertoDepartment of Translational Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Carolina L Haass-KofflerCenter for Alcohol and Addiction Studies, Department of Psychiatry and Human Behavior, Department of Behavioral and Social Sciences, Carney Institute for Brain Sciences, Brown University, Providence, RI, USA.
Roberto CiccocioppoSchool of Pharmacy, Center for Neuroscience, Pharmacology Unit, University of Camerino, Italy.
Douglas J ShefflerCenter for Therapeutics Discovery, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Nazzareno CannellaSchool of Pharmacy, Center for Neuroscience, Pharmacology Unit, University of Camerino, Italy. Electronic address: nazzareno.cannella@unicam.it.

Funding

The Nociceptin ORL1 System: Treatment Target for RelapseR01AA014351 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI Friedbert Weiss · 2004 to 2026
$7.3M
Optimization of Drug-like Properties of CRFBP-CRF2 Negative Allosteric Modulators for Alcohol Use DisorderR01AA030888 · NIAAA · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI DOUGLAS J SHEFFLER · 2023 to 2026
$3.2M
NIAAA NIH HHS R01 AA014351NIAAA NIH HHS R01 AA030888
6 · The paper itself

Abstract

Alcohol Use Disorder (AUD) is a global health concern, with stress playing a crucial role in its development and persistence. Currently, no pharmacotherapies specifically targeting stress are approved for AUD treatment. Neuropeptide S (NPS) plays a dual role in stress regulation, exhibiting both anxiolytic and stress-enhancing effects. While NPS reduces alcohol self-administration (ASA) in alcohol preferring rats, its role in AUD-related stress and anxiety remains unclear. This study investigated the behavioral effects of NPS in male and female Marchigian Sardinian alcohol-preferring (msP) rats. To assess its impact on locomotion, anxiety, and fear memory, we conducted an open-field, an elevated plus maze (EPM), and a fear conditioning (FC) paradigm following intracerebroventricular administration of NPS. Furthermore, we examined the effects of NPS on ASA and yohimbine-induced reinstatement of alcohol-seeking in msP rats. Our results indicate that NPS administration increased locomotor activity in both sexes and selectively alleviated generalized anxiety levels in male rats in the EPM test. In the FC task, administration of NPS immediately after FC test facilitated the extinction of fear memories in females but not in males. Notably, NPS reduced ASA in both female and male rats but did not alter yohimbine-induced reinstatement of alcohol-seeking. In conclusion, NPS modulates anxiety in a sex-dependent manner. Since both alcohol and NPS alleviate anxiety and fear conditioning in msP rats, NPS may reduce alcohol intake by replacing the anxiolytic properties of alcohol. These effects appear to be sex-dependent, with NPS primarily alleviating generalized anxiety in males and facilitating fear extinction in females.

Indexed as

AnxietyConditioning, PsychologicalDrug-Seeking BehaviorEthanolFearNeuropeptidesSex CharacteristicsAnimalsExtinction, PsychologicalFemaleLocomotionMaleRatsSelf AdministrationEthanolNeuropeptidesneuropeptide S, ratAlcoholismAnxietyGenetic predisposition to AUDNeuropeptide SPost-traumatic stress disorderSex-differencesStress

Identifiers

PMID40712753
PMCPMC13198912

What OpenQuestion holds

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LicenceCC BY
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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.