Electroencephalography Biomarkers of α5-GABA Positive Allosteric Modulators in Rodents
Background: Reduced cortical inhibition mediated by GABA (gamma-aminobutyric acid) is reported in depression, anxiety disorders, and aging. A novel positive allosteric modulator that specifically targets the α5-GABAA receptor subunit (α5-PAM), ligand GL-II-73 shows anxiolytic, antidepressant, and pr...
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Elsevier
2025-03-01
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| Series: | Biological Psychiatry Global Open Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667174324001484 |
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| author | Frank Mazza Alexandre Guet-McCreight Thomas D. Prevot Taufik Valiante Etienne Sibille Etay Hay |
| author_facet | Frank Mazza Alexandre Guet-McCreight Thomas D. Prevot Taufik Valiante Etienne Sibille Etay Hay |
| author_sort | Frank Mazza |
| collection | DOAJ |
| description | Background: Reduced cortical inhibition mediated by GABA (gamma-aminobutyric acid) is reported in depression, anxiety disorders, and aging. A novel positive allosteric modulator that specifically targets the α5-GABAA receptor subunit (α5-PAM), ligand GL-II-73 shows anxiolytic, antidepressant, and procognitive effects without the common side effects associated with nonspecific modulation by benzodiazepines such as diazepam, thus suggesting novel therapeutic potential. However, it is unknown whether α5-PAM has detectable signatures in clinically relevant brain electroencephalography (EEG). Methods: We analyzed EEG in 10 freely moving rats at baseline and following injections of α5-PAM (GL-II-73) and diazepam. Results: We showed that α5-PAM specifically decreased theta peak power, whereas diazepam shifted peak power from high to low theta while increasing beta and gamma power. EEG decomposition showed that these effects were periodic and corresponded to changes in theta oscillation event duration. Conclusions: Thus, our study shows that α5-PAM has robust and distinct EEG biomarkers in rodents, indicating that EEG could enable noninvasive monitoring of α5-PAM treatment efficacy. |
| format | Article |
| id | doaj-art-f527220ab3c940eb80a1839289ecc5da |
| institution | Kabale University |
| issn | 2667-1743 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biological Psychiatry Global Open Science |
| spelling | doaj-art-f527220ab3c940eb80a1839289ecc5da2025-02-05T04:32:48ZengElsevierBiological Psychiatry Global Open Science2667-17432025-03-0152100435Electroencephalography Biomarkers of α5-GABA Positive Allosteric Modulators in RodentsFrank Mazza0Alexandre Guet-McCreight1Thomas D. Prevot2Taufik Valiante3Etienne Sibille4Etay Hay5Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, CanadaKrembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, Ontario, CanadaDepartment of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, CanadaKrembil Brain Institute, University Healthy Network, Toronto, Ontario, Canada; Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada; Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Center for Advancing Neurotechnological Innovation to Application, Toronto, Ontario, Canada; Max Planck-University of Toronto Center for Neural Science and Technology, Toronto, Ontario, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, CanadaDepartment of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, CanadaKrembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Address correspondence to Etay Hay, Ph.D.Background: Reduced cortical inhibition mediated by GABA (gamma-aminobutyric acid) is reported in depression, anxiety disorders, and aging. A novel positive allosteric modulator that specifically targets the α5-GABAA receptor subunit (α5-PAM), ligand GL-II-73 shows anxiolytic, antidepressant, and procognitive effects without the common side effects associated with nonspecific modulation by benzodiazepines such as diazepam, thus suggesting novel therapeutic potential. However, it is unknown whether α5-PAM has detectable signatures in clinically relevant brain electroencephalography (EEG). Methods: We analyzed EEG in 10 freely moving rats at baseline and following injections of α5-PAM (GL-II-73) and diazepam. Results: We showed that α5-PAM specifically decreased theta peak power, whereas diazepam shifted peak power from high to low theta while increasing beta and gamma power. EEG decomposition showed that these effects were periodic and corresponded to changes in theta oscillation event duration. Conclusions: Thus, our study shows that α5-PAM has robust and distinct EEG biomarkers in rodents, indicating that EEG could enable noninvasive monitoring of α5-PAM treatment efficacy.http://www.sciencedirect.com/science/article/pii/S2667174324001484BiomarkersDepressionElectroencephalographyInhibitionPharmacologyRodents |
| spellingShingle | Frank Mazza Alexandre Guet-McCreight Thomas D. Prevot Taufik Valiante Etienne Sibille Etay Hay Electroencephalography Biomarkers of α5-GABA Positive Allosteric Modulators in Rodents Biological Psychiatry Global Open Science Biomarkers Depression Electroencephalography Inhibition Pharmacology Rodents |
| title | Electroencephalography Biomarkers of α5-GABA Positive Allosteric Modulators in Rodents |
| title_full | Electroencephalography Biomarkers of α5-GABA Positive Allosteric Modulators in Rodents |
| title_fullStr | Electroencephalography Biomarkers of α5-GABA Positive Allosteric Modulators in Rodents |
| title_full_unstemmed | Electroencephalography Biomarkers of α5-GABA Positive Allosteric Modulators in Rodents |
| title_short | Electroencephalography Biomarkers of α5-GABA Positive Allosteric Modulators in Rodents |
| title_sort | electroencephalography biomarkers of α5 gaba positive allosteric modulators in rodents |
| topic | Biomarkers Depression Electroencephalography Inhibition Pharmacology Rodents |
| url | http://www.sciencedirect.com/science/article/pii/S2667174324001484 |
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