Peptide LCGA-17 Attenuates Behavioral and Neurochemical Deficits in Rodent Models of PTSD and Depression
We have previously described the LCGA-17 peptide as a novel anxiolytic and antidepressant candidate that acts through the α2δ VGCC (voltage-gated calcium channel) subunit with putative synergism with GABA-A receptors. The current study tested the potential efficacy of acute and chronic intranasal (i...
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| Format: | Article |
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MDPI AG
2022-04-01
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| Online Access: | https://www.mdpi.com/1424-8247/15/4/462 |
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| author | Anton V. Malyshev Iuliia A. Sukhanova Valeria M. Ushakova Yana A. Zorkina Olga V. Abramova Anna Y. Morozova Eugene A. Zubkov Nikita A. Mitkin Vsevolod V. Pavshintsev Igor I. Doronin Vasilina R. Gedzun Gennady A. Babkin Sergio A. Sanchez Miah D. Baker Colin N. Haile |
| author_facet | Anton V. Malyshev Iuliia A. Sukhanova Valeria M. Ushakova Yana A. Zorkina Olga V. Abramova Anna Y. Morozova Eugene A. Zubkov Nikita A. Mitkin Vsevolod V. Pavshintsev Igor I. Doronin Vasilina R. Gedzun Gennady A. Babkin Sergio A. Sanchez Miah D. Baker Colin N. Haile |
| author_sort | Anton V. Malyshev |
| collection | DOAJ |
| description | We have previously described the LCGA-17 peptide as a novel anxiolytic and antidepressant candidate that acts through the α2δ VGCC (voltage-gated calcium channel) subunit with putative synergism with GABA-A receptors. The current study tested the potential efficacy of acute and chronic intranasal (i.n.) LCGA-17 (0.05 mg/kg and 0.5 mg/kg) in rats on predator odor-induced conditioned place aversion (POCPA), a model of post-traumatic stress disorder (PTSD), and chronic unpredictable stress (CUS) that produce a range of behavioral and physiological changes that parallel symptoms of depression in humans. CUS and LCGA-17 treatment effects were tested in the sucrose preference (SPT) social interaction (SI), female urine sniffing (FUST), novelty-suppressed feeding (NSFT), and forced swim (FST) tests. Analysis of the catecholamines content in brain structures after CUS was carried out using HPLC. The efficacy of i.n. LCGA-17 was also assessed using the Elevated plus-maze (EPM) and FST. Acute LCGA-17 administration showed anxiolytic and antidepressant effects in EPM and FST, similar to diazepam and ketamine, respectively. In the POCPA study, LCGA-17 significantly reduced place aversion, with efficacy greater than doxazosin. After CUS, chronic LCGA-17 administration reversed stress-induced alterations in numerous behavioral tests (SI, FUST, SPT, and FST), producing significant anxiolytic and antidepressant effects. Finally, LCGA-17 restored the norepinephrine levels in the hippocampus following stress. Together, these results support the further development of the LCGA-17 peptide as a rapid-acting anxiolytic and antidepressant. |
| first_indexed | 2024-03-09T10:31:36Z |
| format | Article |
| id | doaj.art-eba1a1865ee04e8eb42573053d2d6eb5 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T10:31:36Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-eba1a1865ee04e8eb42573053d2d6eb52023-12-01T21:18:12ZengMDPI AGPharmaceuticals1424-82472022-04-0115446210.3390/ph15040462Peptide LCGA-17 Attenuates Behavioral and Neurochemical Deficits in Rodent Models of PTSD and DepressionAnton V. Malyshev0Iuliia A. Sukhanova1Valeria M. Ushakova2Yana A. Zorkina3Olga V. Abramova4Anna Y. Morozova5Eugene A. Zubkov6Nikita A. Mitkin7Vsevolod V. Pavshintsev8Igor I. Doronin9Vasilina R. Gedzun10Gennady A. Babkin11Sergio A. Sanchez12Miah D. Baker13Colin N. Haile14Lactocore Inc., Newton, MA 02460, USALactocore Inc., Newton, MA 02460, USADepartment of Basic and Applied Neurobiology, V.P. Serbsky Federal Medical Research Centre of Psychiatry and Narcology, 119034 Moscow, RussiaDepartment of Basic and Applied Neurobiology, V.P. Serbsky Federal Medical Research Centre of Psychiatry and Narcology, 119034 Moscow, RussiaDepartment of Basic and Applied Neurobiology, V.P. Serbsky Federal Medical Research Centre of Psychiatry and Narcology, 119034 Moscow, RussiaDepartment of Basic and Applied Neurobiology, V.P. Serbsky Federal Medical Research Centre of Psychiatry and Narcology, 119034 Moscow, RussiaDepartment of Basic and Applied Neurobiology, V.P. Serbsky Federal Medical Research Centre of Psychiatry and Narcology, 119034 Moscow, RussiaLactocore Inc., Newton, MA 02460, USALactocore Inc., Newton, MA 02460, USALactocore Inc., Newton, MA 02460, USALactocore Inc., Newton, MA 02460, USALactocore Inc., Newton, MA 02460, USADepartment of Psychology/TIMES, University of Houston, Houston, TX 77204, USADepartment of Psychology/TIMES, University of Houston, Houston, TX 77204, USADepartment of Psychology/TIMES, University of Houston, Houston, TX 77204, USAWe have previously described the LCGA-17 peptide as a novel anxiolytic and antidepressant candidate that acts through the α2δ VGCC (voltage-gated calcium channel) subunit with putative synergism with GABA-A receptors. The current study tested the potential efficacy of acute and chronic intranasal (i.n.) LCGA-17 (0.05 mg/kg and 0.5 mg/kg) in rats on predator odor-induced conditioned place aversion (POCPA), a model of post-traumatic stress disorder (PTSD), and chronic unpredictable stress (CUS) that produce a range of behavioral and physiological changes that parallel symptoms of depression in humans. CUS and LCGA-17 treatment effects were tested in the sucrose preference (SPT) social interaction (SI), female urine sniffing (FUST), novelty-suppressed feeding (NSFT), and forced swim (FST) tests. Analysis of the catecholamines content in brain structures after CUS was carried out using HPLC. The efficacy of i.n. LCGA-17 was also assessed using the Elevated plus-maze (EPM) and FST. Acute LCGA-17 administration showed anxiolytic and antidepressant effects in EPM and FST, similar to diazepam and ketamine, respectively. In the POCPA study, LCGA-17 significantly reduced place aversion, with efficacy greater than doxazosin. After CUS, chronic LCGA-17 administration reversed stress-induced alterations in numerous behavioral tests (SI, FUST, SPT, and FST), producing significant anxiolytic and antidepressant effects. Finally, LCGA-17 restored the norepinephrine levels in the hippocampus following stress. Together, these results support the further development of the LCGA-17 peptide as a rapid-acting anxiolytic and antidepressant.https://www.mdpi.com/1424-8247/15/4/462chronic stressnovel treatmentpeptide drugbiogenic amines |
| spellingShingle | Anton V. Malyshev Iuliia A. Sukhanova Valeria M. Ushakova Yana A. Zorkina Olga V. Abramova Anna Y. Morozova Eugene A. Zubkov Nikita A. Mitkin Vsevolod V. Pavshintsev Igor I. Doronin Vasilina R. Gedzun Gennady A. Babkin Sergio A. Sanchez Miah D. Baker Colin N. Haile Peptide LCGA-17 Attenuates Behavioral and Neurochemical Deficits in Rodent Models of PTSD and Depression Pharmaceuticals chronic stress novel treatment peptide drug biogenic amines |
| title | Peptide LCGA-17 Attenuates Behavioral and Neurochemical Deficits in Rodent Models of PTSD and Depression |
| title_full | Peptide LCGA-17 Attenuates Behavioral and Neurochemical Deficits in Rodent Models of PTSD and Depression |
| title_fullStr | Peptide LCGA-17 Attenuates Behavioral and Neurochemical Deficits in Rodent Models of PTSD and Depression |
| title_full_unstemmed | Peptide LCGA-17 Attenuates Behavioral and Neurochemical Deficits in Rodent Models of PTSD and Depression |
| title_short | Peptide LCGA-17 Attenuates Behavioral and Neurochemical Deficits in Rodent Models of PTSD and Depression |
| title_sort | peptide lcga 17 attenuates behavioral and neurochemical deficits in rodent models of ptsd and depression |
| topic | chronic stress novel treatment peptide drug biogenic amines |
| url | https://www.mdpi.com/1424-8247/15/4/462 |
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