Mechanism-Dependent Effects of the α5 GABAA Receptor Negative Allosteric Modulator Basmisanil on Spatial Memory
- 1Faculty of Medicine, Pharmacology, Clinical Pharmacology and Pharmacotherapy Discipline, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- 2Faculty of Medical Engineering, National University of Science and Technology POLITEHNICA Bucharest, 060042 Bucharest, Romania
Abstract
Cognitive impairment may arise through multiple pathophysiological mechanisms, including altered GABAergic neurotransmission, cholinergic dysfunction, and neuroinflammation. This study investigated whether basmisanil, a selective negative allosteric modulator of α5-containing GABAA receptors, attenuates spatial memory impairment induced by diazepam, trihexyphenidyl (THP), or lipopolysaccharide (LPS). Adult male Wistar rats were assigned to three experimental models of memory impairment, each comprising four treatment groups (control, inducing agent, basmisanil, and inducing agent plus basmisanil; n = 7/group). Spatial memory was assessed using the two-trial Y-maze paradigm. The primary outcome (Time Index U) was analyzed using two-way factorial general linear models with sensitivity analyses. Significant interactions between the inducing agent and basmisanil were observed in the diazepam and LPS models, indicating attenuation of memory impairment following basmisanil coadministration, whereas no significant interaction was detected in the THP model. The largest estimated recovery effect was observed in the diazepam model, followed by the LPS model and the THP model, although cross-model comparisons were not statistically significant. Basmisanil alone did not enhance baseline memory performance. These findings indicate that the behavioral effects of α5-containing GABAA receptor modulation are mechanism-dependent and support further investigation of selective α5 negative allosteric modulators for benzodiazepine-associated memory impairment.
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BibTeX
@article{moraru2026mechanismdependent,
title = {{Mechanism-Dependent Effects of the α5 GABAA Receptor Negative Allosteric Modulator Basmisanil on Spatial Memory}},
author = {Miruna Valeria Moraru and Aurelian Zugravu and Aurelia Cristiana Barbu and Smaranda Stoleru and Cristina Isabel Viorica Ghiță and Adrian-Florentin Dragomir and Andrei Stoian and Laurentiu-Nicolae Ciuca and Dragos Constantin Lunca and Clara Maria Stoleru and Oana Andreia Coman and Ion Fulga},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16101429},
url = {https://www.mdpi.com/2218-273X/16/10/1429},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mechanism-Dependent Effects of the α5 GABAA Receptor Negative Allosteric Modulator Basmisanil on Spatial Memory
AU - Miruna Valeria Moraru
AU - Aurelian Zugravu
AU - Aurelia Cristiana Barbu
AU - Smaranda Stoleru
AU - Cristina Isabel Viorica Ghiță
AU - Adrian-Florentin Dragomir
AU - Andrei Stoian
AU - Laurentiu-Nicolae Ciuca
AU - Dragos Constantin Lunca
AU - Clara Maria Stoleru
AU - Oana Andreia Coman
AU - Ion Fulga
PY - 2026
DA - 2026/10/01
JO - Biomolecules
DO - 10.3390/biom16101429
UR - https://www.mdpi.com/2218-273X/16/10/1429
AB - Cognitive impairment may arise through multiple pathophysiological mechanisms, including altered GABAergic neurotransmission, cholinergic dysfunction, and neuroinflammation. This study investigated whether basmisanil, a selective negative allosteric modulator of α5-containing GABAA receptors, attenuates spatial memory impairment induced by diazepam, trihexyphenidyl (THP), or lipopolysaccharide (LPS). Adult male Wistar rats were assigned to three experimental models of memory impairment, each comprising four treatment groups (control, inducing agent, basmisanil, and inducing agent plus basmisanil; n = 7/group). Spatial memory was assessed using the two-trial Y-maze paradigm. The primary outcome (Time Index U) was analyzed using two-way factorial general linear models with sensitivity analyses. Significant interactions between the inducing agent and basmisanil were observed in the diazepam and LPS models, indicating attenuation of memory impairment following basmisanil coadministration, whereas no significant interaction was detected in the THP model. The largest estimated recovery effect was observed in the diazepam model, followed by the LPS model and the THP model, although cross-model comparisons were not statistically significant. Basmisanil alone did not enhance baseline memory performance. These findings indicate that the behavioral effects of α5-containing GABAA receptor modulation are mechanism-dependent and support further investigation of selective α5 negative allosteric modulators for benzodiazepine-associated memory impairment.
SN - 2218-273X
ER -