Evidence map›Paper›PMID 40198329›Full record

ArticlePsychopharmacology2025

Sex specific effects of ketamine, but not other glutamate receptor modulators, on ethanol self-administration and reinstatement of ethanol seeking in rats.

Megan L Bertholomey, Camryn Forbes, Bryan D McElroy, Mary M Torregrossa

Abstract read
In one paragraph

Article in Psychopharmacology, 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

4 authors.

Megan L BertholomeyDepartment of Psychiatry, Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, 15219, USA.
Camryn ForbesDepartment of Psychiatry, Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, 15219, USA.
Bryan D McElroyDepartment of Psychiatry, Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, 15219, USA.
Mary M TorregrossaDepartment of Psychiatry, Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, 15219, USA. torregrossam@upmc.edu.ORCID http://orcid.org/0000-0003-2083-0231

Funding

Subject Management and BiobankingP50DA046346 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Daniel J. Buysse, Colleen A McClung · 2020 to 2026
$23.4M
Investigating mechanisms mediating enhanced THC reinforcement by nicotineR01DA058955 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Mary M Torregrossa · 2023 to 2026
$2.1M
Mechanistic studies of alcohol-sleep interactionsR01AA028145 · NIAAA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HUANG, YANHUA H, TORREGROSSA, MARY M · 2019 to 2023
$2.0M
Mechanisms underlying sex differences in stress-induced alcohol seekingR01AA028215 · NIAAA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TORREGROSSA, MARY M · 2020 to 2024
$1.9M
A novel role for midbrain glutamate co-transmitting neurons in alcohol drinking and motivated behaviorsR21AA028800 · NIAAA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FREYBERG, ZACHARY, LOGAN, RYAN W · 2021 to 2022
$446k
Phosphoproteomic Identification of Low Dose Alcohol TargetsR21AA025547 · NIAAA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TORREGROSSA, MARY M · 2016 to 2017
$426k
Brackenridge Fellowship Brackenridge FellowshipDSF Charitable Foundation DSF Charitable FoundationNIAAA NIH HHS R01 AA028145NIAAA NIH HHS R01AA028145NIAAA NIH HHS R01 AA028215NIAAA NIH HHS R01AA028215NIAAA NIH HHS R21 AA025547NIAAA NIH HHS R21AA025547NIAAA NIH HHS R21 AA028800NIAAA NIH HHS R21AA028800NIDA NIH HHS P50 DA046346NIDA NIH HHS P50DA046346NIDA NIH HHS R01 DA058955
6 · The paper itself

Abstract

rationaleAlcohol use and major depressive disorder are frequently comorbid, with individuals diagnosed with a substance use disorder being nearly three times as likely to have major depression. Poor treatment responses are found for both disorders and are further complicated when they co-occur, underscoring the need for better therapies. One potential candidate is ketamine, which has been shown to have rapid and long-lasting effects in individuals with treatment-resistant depression and, in some studies, reduces drinking in alcohol use disorder. However, though women are more likely to have this comorbidity, few studies have examined sex-specific effects of ketamine on alcohol drinking, nor have studies assessed the potential for ketamine to reduce reinstatement of alcohol seeking.

objectivesThe primary goal of the present studies was to determine the effects of ketamine on alcohol-motivated behaviors in male and female rats, including in a model of stress + cue-induced reinstatement of alcohol seeking using yohimbine (YOH).

resultsWe found a selective reduction in alcohol self-administration and YOH + cue-induced reinstatement in females, but not males at a dose of 10 mg/kg ketamine. However, the same dose of ketamine was effective in reducing YOH + cue-induced reinstatement of saccharin seeking in both sexes. In addition, a different NMDAR antagonist, memantine, was effective in reducing alcohol seeking in both sexes, while the ketamine metabolite hydroxynorketamine (HNK) had no effects.

conclusionsIn summary, these data suggest that antagonism of NMDARs may be effective in reducing stress-related alcohol seeking, but that ketamine has unique properties that lead to female-specific effects on alcohol seeking.

Indexed as

Alcohol DrinkingDrug-Seeking BehaviorEthanolExcitatory Amino Acid AntagonistsKetamineAnimalsCuesDose-Response Relationship, DrugFemaleMaleRatsRats, Sprague-DawleySelf AdministrationSex CharacteristicsSex FactorsYohimbineEthanolExcitatory Amino Acid AntagonistsKetamineYohimbine2R,6R hydroxynorketamineAlcoholAMPA receptorKetamineMemantineNMDA receptorReinstatementSex differencesStress

Identifiers

PMID40198329
PMCPMC12614745

What OpenQuestion holds

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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.