Evidence map›Paper›PMID 40774149›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2025

Using a rich-lean transition procedure to evaluate putative antianxiety medications.

Forrest Toegel, Cory Toegel, James K Rowlett, Josh A Woods, Carlos Austin Zamarripa, William S Doyle, Kevin B Freeman, Sally L Huskinson

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

8 authors.

Forrest ToegelDepartment of Psychological Science, Northern Michigan University, Marquette, Michigan.
Cory ToegelDepartment of Psychological Science, Northern Michigan University, Marquette, Michigan.
James K RowlettDivision of Neurobiology and Behavior Research, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi; Program in Neuroscience, University of Mississippi Medical Center, Jackson, Mississippi; Center for Innovation and Discovery in Addictions, University of Mississippi Medical Center, Jackson, Mississippi.
Josh A WoodsDivision of Neurobiology and Behavior Research, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi.
Carlos Austin ZamarripaBehavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, Baltimore, Maryland.
William S DoyleProgram in Neuroscience, University of Mississippi Medical Center, Jackson, Mississippi.
Kevin B FreemanDivision of Neurobiology and Behavior Research, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi; Program in Neuroscience, University of Mississippi Medical Center, Jackson, Mississippi; Center for Innovation and Discovery in Addictions, University of Mississippi Medical Center, Jackson, Mississippi.
Sally L HuskinsonDivision of Neurobiology and Behavior Research, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi; Program in Neuroscience, University of Mississippi Medical Center, Jackson, Mississippi; Center for Innovation and Discovery in Addictions, University of Mississippi Medical Center, Jackson, Mississippi. Electronic address: shuskinson@umc.edu.

Funding

ANXIOLYTIC EFFECTS AND ABUSE OF BZ RECEPTOR LIGANDSR01DA011792 · NIDA · UNIVERSITY OF MISSISSIPPI MED CTR · PI ROWLETT, JAMES K · 1998 to 2024
$7.8M
Tolerance and Physical Dependence after Chronic Benzodiazepine TreatmentR01DA043204 · NIDA · UNIVERSITY OF MISSISSIPPI MED CTR · PI JAMES K ROWLETT · 2017 to 2026
$4.3M
Benzodiazepine Choice and Polydrug UseR01DA054177 · NIDA · UNIVERSITY OF MISSISSIPPI MED CTR · PI Sally L Huskinson · 2022 to 2026
$2.5M
Unpredictable availability as a determinant of drug-related outcomesR01DA045011 · NIDA · UNIVERSITY OF MISSISSIPPI MED CTR · PI HUSKINSON, SALLY · 2018 to 2022
$1.8M
NIDA NIH HHS R01 DA011792NIDA NIH HHS R01 DA043204NIDA NIH HHS R01 DA045011NIDA NIH HHS R01 DA054177
6 · The paper itself

Abstract

Potential antianxiety medications are commonly assessed by measuring their ability to increase behavior that is suppressed by aversive events like shock. These procedures have good predictive validity, but they also have practical limitations, particularly in nonhuman primates. The goal of the current experiment was to determine the feasibility of a different procedure to evaluate potential antianxiety medications without using shock. In prior research, arranging transitions from favorable to unfavorable schedules of positive reinforcement (rich-lean transitions) reliably disrupts operant behavior, and these disruptions can be ameliorated via benzodiazepine administration. We evaluated the suitability of a rich-lean transition procedure for preclinical evaluation of putative antianxiety medications. Adult rhesus monkeys' lever presses were reinforced using a 2-component multiple schedule with equivalent fixed-ratio requirements. Components were differentially signaled by colored stimulus lights. Completing a lean component produced 1 food pellet, and completing a rich component produced 4 food pellets. Sessions consisted of 41 components arranged irregularly to produce 10 iterations of 4 transition types: lean-lean, lean-rich, rich-lean, and rich-rich. As in the prior research, extended pausing was observed in rich-lean transitions. Acute administration of benzodiazepines (midazolam, alprazolam) and an imidazotriazine (TPA-023B) selectively reduced pausing in rich-lean transitions, a behavioral effect consistent with clinically effective antianxiety drugs in other preclinical anxiolysis procedures. Morphine and (+)amphetamine selectively increased rich-lean pausing, an effect consistent with an anxiogenic response in other anxiolysis procedures. Altogether, our results indicate that the rich-lean procedure has utility in the assessment putative antianxiety medications. SIGNIFICANCE STATEMENT: Transitions from favorable to unfavorable (ie, rich-lean) schedules of reinforcement reliably disrupts operant behavior, and these disruptions can be ameliorated via benzodiazepine administration. Our results indicate that the rich-lean transition procedure has utility in the assessment of putative antianxiety medications.

Indexed as

Anti-Anxiety AgentsConditioning, OperantAnimalsBehavior, AnimalBenzodiazepinesDrug Evaluation, PreclinicalFemaleMacaca mulattaMaleReinforcement ScheduleAnti-Anxiety AgentsBenzodiazepinesAnxiolysisFixed-ratio schedulesPausingRhesus monkeysRich-lean transitions

Identifiers

PMID40774149
PMCPMC12558168

What OpenQuestion holds

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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.