Evidence map›Paper›PMID 42218133›Full record

ArticleTranslational psychiatry2026

Nociceptin/orphanin FQ receptor agonism attenuates behavioral and neural responses to conditioned aversive stimuli.

Kwang-Hyun Hur, Diego A Pizzagalli, Jessi Stover, Kenroy Cayetano, Stephen J Kohut

Abstract read
In one paragraph

Article in Translational psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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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3 · Its place in the literature

Who cites it

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No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Kwang-Hyun HurDepartment of Psychiatry, Harvard Medical School, Boston, MA, USA.
Diego A PizzagalliDepartment of Psychiatry, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7772-1143
Jessi StoverDepartment of Psychiatry, Harvard Medical School, Boston, MA, USA.
Kenroy CayetanoMcLean Imaging Center, McLean Hospital, Belmont, MA, USA.
Stephen J KohutDepartment of Psychiatry, Harvard Medical School, Boston, MA, USA. skohut@mclean.harvard.edu.ORCID http://orcid.org/0000-0002-6906-8818

Funding

Project 4_Bruchas : Circuit-level Approaches for Dissecting Approach/Avoidance Behaviors Mediated by Nociceptin Systems in MiceP50MH119467 · NIMH · MCLEAN HOSPITAL · PI FRANK, MICHAEL J. · 2020 to 2024
$15.9M
Translational models of brain activation patterns during nicotine self-administration and reinstatementK01DA039306 · NIDA · MCLEAN HOSPITAL · PI KOHUT, STEPHEN JOHN · 2015 to 2019
$867k
NIDA NIH HHS K01 DA039306NIMH NIH HHS P50 MH119467U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) P50MH119467-04
6 · The paper itself

Abstract

The nociceptin/orphanin FQ peptide (NOP) receptor has emerged as a promising anxiolytic target, as its activation has been shown to reduce anxiety-related behaviors in rodents. However, the mechanisms underlying these effects are not well understood. Here, we investigated the effects of the selective NOP receptor agonist SCH-221510 (0.01-0.1 mg/kg, IM) on behavioral and neural responses to aversive stimuli in squirrel monkeys (n = 3). Subjects underwent Pavlovian fear conditioning, wherein a visual conditioned stimulus (CS) was paired with the presentation of an aversive stimulus. Event-related functional magnetic resonance imaging (fMRI) was conducted in awake subjects to evaluate CS-evoked neural responses. Behavioral and neural responses to the CS were assessed across three experimental phases: pre-conditioning (Pre-C), post-conditioning (Post-C), and Post-C with SCH-221510 administration. In behavioral assessments, CS presentation during Post-C elicited a robust suppression of ongoing operant responding, which was absent during Pre-C and significantly attenuated by SCH-221510 treatment (0.1 mg/kg). fMRI results revealed that, relative to Pre-C, CS presentation during Post-C was associated with increased BOLD activity in brain regions previously implicated in fear processing (e.g., amygdala), expression and regulation (e.g., prefrontal cortex; PFC), as well as sensory integration (e.g., visual cortex). Critically, SCH-221510 (0.1 mg/kg) administration significantly attenuated CS-induced neural activation in these regions. Furthermore, resting-state functional connectivity analysis revealed that SCH-221510 administration decreased connectivity between PFC and amygdala, while enhancing connectivity among PFC subregions. Collectively, these findings suggest that NOP receptor agonism may attenuate conditioned responses to aversive stimuli by modulating functional interactions within a PFC-amygdala circuit.

Indexed as

Behavior, AnimalBrainConditioning, ClassicalFearReceptors, OpioidAmygdalaAnimalsMagnetic Resonance ImagingMaleNociceptin ReceptorPrefrontal CortexNociceptin ReceptorReceptors, Opioid

Identifiers

PMID42218133
PMCPMC13434006

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.