Evidence map›Paper›PMID 40601035›Full record

ArticlePsychopharmacology2026

Depleting retinoic acid synthesis in the nucleus accumbens shell produces a protective phenotype for emotional reactivity and drug-taking in rats.

Yorkiris Mármol Contreras, Nolan M Dvorak, Cynthia M Tapia, Roxana Zaman, Jyothika Annareddy, Yves Balikosa, Nikita S Gupta, Alex P Rader, Tileena E S Vasquez, Shyny Koshy and 4 more

Abstract read
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In one paragraph

Article in Psychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

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

2 citing papers in PubMed.

  1. Review
  2. 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

14 authors.

Yorkiris Mármol ContrerasDepartment of Pharmacology and Toxicology, The University of Texas Medical Branch, 301 University Dr., Medical Research Bldg 7.102c, Galveston, TX, 77555, USA.
Nolan M DvorakDepartment of Pharmacology and Toxicology, The University of Texas Medical Branch, 301 University Dr., Medical Research Bldg 7.102c, Galveston, TX, 77555, USA.
Cynthia M TapiaDepartment of Pharmacology and Toxicology, The University of Texas Medical Branch, 301 University Dr., Medical Research Bldg 7.102c, Galveston, TX, 77555, USA.
Roxana ZamanJohn Sealy School of Medicine, The University of Texas Medical Branch, Galveston, TX, USA.
Jyothika AnnareddyJohn Sealy School of Medicine, The University of Texas Medical Branch, Galveston, TX, USA.
Yves BalikosaJohn Sealy School of Medicine, The University of Texas Medical Branch, Galveston, TX, USA.
Nikita S GuptaDepartment of Pharmacology and Toxicology, The University of Texas Medical Branch, 301 University Dr., Medical Research Bldg 7.102c, Galveston, TX, 77555, USA.
Alex P RaderDepartment of Pharmacology and Toxicology, The University of Texas Medical Branch, 301 University Dr., Medical Research Bldg 7.102c, Galveston, TX, 77555, USA.
Tileena E S VasquezDepartment of Pharmacology and Toxicology, The University of Texas Medical Branch, 301 University Dr., Medical Research Bldg 7.102c, Galveston, TX, 77555, USA.
Shyny KoshyDepartment of Pharmacology and Toxicology, The University of Texas Medical Branch, 301 University Dr., Medical Research Bldg 7.102c, Galveston, TX, 77555, USA.
Dingge LiDepartment of Pharmacology and Toxicology, The University of Texas Medical Branch, 301 University Dr., Medical Research Bldg 7.102c, Galveston, TX, 77555, USA.
Varun K BalajiDepartment of Pharmacology and Toxicology, The University of Texas Medical Branch, 301 University Dr., Medical Research Bldg 7.102c, Galveston, TX, 77555, USA.
Fernanda LaezzaDepartment of Pharmacology and Toxicology, The University of Texas Medical Branch, 301 University Dr., Medical Research Bldg 7.102c, Galveston, TX, 77555, USA.
Thomas A GreenDepartment of Pharmacology and Toxicology, The University of Texas Medical Branch, 301 University Dr., Medical Research Bldg 7.102c, Galveston, TX, 77555, USA. thgreen@utmb.edu.

Funding

HOUSTON AREA MOLECULAR BIOPHYSICS TRAINING PROGRAMT32GM008280 · NIGMS · RICE UNIVERSITY · PI WENSEL, THEODORE G · 1988 to 2023
$8.0M
Translational Explorations in Substance Use DisordersT32DA007287 · NIDA · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI Kathryn A. Cunningham, Jonathan Dean Hommel · 1994 to 2026
$4.7M
Frustration effects on drug takingR01DA060221 · NIDA · UNIVERSITY OF TEXAS MED BR GALVESTON · PI Thomas Arthur Green · 2024 to 2026
$1.2M
NIDA NIH HHS DA007287NIDA NIH HHS DA047102NIDA NIH HHS DA060221NIDA NIH HHS R01 DA060221NIDA NIH HHS T32 DA007287NIH HHS T32GM008280
6 · The paper itself

Abstract

rationaleIn previous work, a convergent transcriptomic approach strongly suggested a role for retinoic acid (RA) in controlling the emotion- and reward-related functions of the nucleus accumbens shell (NAcSh).

objectiveHere, we causally assess the role of NAcSh RA in controlling anxiety-, emotion-, and reward-related behavior in rats and explore cellular mechanisms that may underlie this phenotype.

methodsRats underwent bilateral knockdown of the retinoic acid synthesis enzyme Aldh1a1 in the NAcSh. Anxiety-related behavior was assessed using open-field exploration, elevated plus maze, and sucrose neophobia tests. Emotion-related behavior was assessed via sucrose preference, post-isolation social contact, and forced swim tests. Animals were subsequently allowed to self-administer fentanyl to assess reward- and frustration-related behavior. In parallel, electrophysiological testing of medium spiny neurons (MSNs) in the NAcSh was used to explore the role of RA in NAcSh cellular function.

resultsWe observed an anxiety-vulnerable, depression-resilient phenotype in knockdown animals compared to controls. During operant tasks, knockdown animals took fewer fentanyl infusions during FR5 maintenance and showed decreased demand intensity in behavioral economics sessions. Finally, electrophysiological assessment of NAcSh MSNs revealed attenuated excitability following Aldh1a1 knockdown. Altogether, our findings reveal a key role for NAcSh RA signaling in determining emotional resilience and drug-taking, likely via decreased MSN excitability.

conclusionsOur results posit the RA synthesis enzyme Aldh1a1 as a promising therapeutic target for depression-, frustration-, and addiction-associated disorders. This is the first report linking RA to frustrative nonreward, the NAcSh to operant frustration, and RA to fentanyl drug-taking behavior.

Indexed as

Drug-Seeking BehaviorEmotionsNucleus AccumbensTretinoinAldehyde Dehydrogenase 1 FamilyAnimalsAnxietyBehavior, AnimalFentanylGene Knockdown TechniquesMalePhenotypeRatsRats, Sprague-DawleyRetinal DehydrogenaseRewardAldehyde Dehydrogenase 1 FamilyAldh1a1 protein, ratFentanylRetinal DehydrogenaseTretinoinAddictionDrug abuse liabilityDrug takingElectrophysiologyEmotionalityEvoked potentialsFrustrative non-rewardFrustrative nonrewardMotivationRetinoic acidVitamin A deficiency

Identifiers

PMID40601035
PMCPMC13019352

What Socratic 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 Socratic graph.