Evidence map›Paper›PMID 42113235›Full record

ArticlePsychopharmacology2026

Influences of subtle NMDA receptor blockade and allosteric modulation of α5 GABAA receptors on reward-related impulsivity in rats.

Jovana Aranđelović, Bojan Batinić, Dishary Sharmin, Danijela Milenković, Đorđe Đorović, V V N Phani Babu Tiruveedhula, James M Cook, Miroslav M Savić

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Article in Psychopharmacology, 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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1 · What the graph read from it

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5 · Who and what money

Authors and funding

8 authors.

Jovana AranđelovićDepartment of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Bojan BatinićDepartment of Physiology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Dishary SharminDepartment of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
Danijela MilenkovićDepartment of Physics and Mathematics, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Đorđe ĐorovićInstitute of Anatomy Niko Miljanic, University of Belgrade - School of Medicine, Belgrade, Serbia.
V V N Phani Babu TiruveedhulaDepartment of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
James M CookDepartment of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
Miroslav M SavićDepartment of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia. miroslav@pharmacy.bg.ac.rs.ORCID http://orcid.org/0000-0002-6934-9193

Funding

Design of New Therapeutic Agents to Treat SchizophreniaR01MH096463 · NIMH · UNIVERSITY OF WISCONSIN MILWAUKEE · PI COOK, JAMES M · 2013 to 2017
$1.9M
Synthesis of Alpha2/Alpha3 GABA Agonists to Treat Neuropathic PainR01NS076517 · NINDS · UNIVERSITY OF WISCONSIN MILWAUKEE · PI COOK, JAMES M · 2012 to 2015
$1.3M
Innovative Medicines Initiative 821528National Science Foundation CHE- 1625735 to JMCNIMH NIH HHS R01 MH096463NINDS NIH HHS R01 NS076517Science Fund of the Republic of Serbia 7749108
6 · The paper itself

Abstract

rationaleAvailable data suggest that α5GABAA receptors play an important role in the regulation of impulsive behavior.

objectivesWe studied the effect of selective positive and negative modulation of α5GABAA receptors, alone and in combination with NMDA receptor blockade, on different areas of impulsivity in rats.

methodsA modified variable delay-to signal (VDS) paradigm in touchscreen chambers was introduced and validated. Male rats pretrained in the VDS protocol were treated with MK-801 at different doses and subjected to a test consisting of 20 initial 6-second delay trials, followed by 60 variable delay trials of 9-15 s, and finally 20 6-second delay trials. The dose of 0.05 mg/kg MK-801 in combination with 10 mg/kg GL-II-73 or 5 mg/kg PWZ-029 was tested in the VDS paradigm and the elevated plus maze to assess the potential of their interaction in the areas of impulsivity and anxiety, respectively.

resultsThe principal component analysis revealed three dimensions of impulsivity, assignable to motor impulsivity, delay intolerance and reflective impulsivity. Delay intolerance and reflective impulsivity elicited by 0.05 mg/kg MK-801 were more likely to affect high-impulsive rats than low-impulsive rats. The low MK-801 dose did not replicate the impulsive effect in the interaction experiment, while the addition of GL-II-73 resulted in significant delay intolerance. The same doses of tested compounds did not affect emotional reactivity.

conclusionsThe proimpulsive effect of positive modulation of α5GABAA receptors on delay intolerance can be interpreted as a kind of cognitive influence, but also as favoring reward seeking due to increased motivation, which requires further research.

Indexed as

GL-II-73ImpulsivityMK-801Principal component analysisSprague-Dawley ratsVariable delay-to-signal paradigmα5 GABAA receptors

Identifiers

PMID42113235

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