Acute Ketamine Facilitates Fear Memory Extinction in a Rat Model of PTSD Along With Restoring Glutamatergic Alterations and Dendritic Atrophy in the Prefrontal Cortex
Stress represents a major risk factor for psychiatric disorders, including post-traumatic stress disorder (PTSD). Recently, we dissected the destabilizing effects of acute stress on the excitatory glutamate system in the prefrontal cortex (PFC). Here, we assessed the effects of single subanesthetic...
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.759626/full |
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| author | Nathalie Sala Caterina Paoli Caterina Paoli Tiziana Bonifacino Jessica Mingardi Emanuele Schiavon Luca La Via Marco Milanese Paolo Tornese Ashok K. Datusalia Ashok K. Datusalia Jessica Rosa Jessica Rosa Roberta Facchinetti Giulia Frumento Giulia Carini Floramarida Salerno Scarzella Caterina Scuderi Lia Forti Alessandro Barbon Giambattista Bonanno Giambattista Bonanno Maurizio Popoli Laura Musazzi |
| author_facet | Nathalie Sala Caterina Paoli Caterina Paoli Tiziana Bonifacino Jessica Mingardi Emanuele Schiavon Luca La Via Marco Milanese Paolo Tornese Ashok K. Datusalia Ashok K. Datusalia Jessica Rosa Jessica Rosa Roberta Facchinetti Giulia Frumento Giulia Carini Floramarida Salerno Scarzella Caterina Scuderi Lia Forti Alessandro Barbon Giambattista Bonanno Giambattista Bonanno Maurizio Popoli Laura Musazzi |
| author_sort | Nathalie Sala |
| collection | DOAJ |
| description | Stress represents a major risk factor for psychiatric disorders, including post-traumatic stress disorder (PTSD). Recently, we dissected the destabilizing effects of acute stress on the excitatory glutamate system in the prefrontal cortex (PFC). Here, we assessed the effects of single subanesthetic administration of ketamine (10 mg/kg) on glutamate transmission and dendritic arborization in the PFC of footshock (FS)-stressed rats, along with changes in depressive, anxious, and fear extinction behaviors. We found that ketamine, while inducing a mild increase of glutamate release in the PFC of naïve rats, blocked the acute stress-induced enhancement of glutamate release when administered 24 or 72 h before or 6 h after FS. Accordingly, the treatment with ketamine 6 h after FS also reduced the stress-dependent increase of spontaneous excitatory postsynaptic current (sEPSC) amplitude in prelimbic (PL)-PFC. At the same time, ketamine injection 6 h after FS was found to rescue apical dendritic retraction of pyramidal neurons induced by acute stress in PL-PFC and facilitated contextual fear extinction. These results show rapid effects of ketamine in animals subjected to acute FS, in line with previous studies suggesting a therapeutic action of the drug in PTSD models. Our data are consistent with a mechanism of ketamine involving re-establishment of synaptic homeostasis, through restoration of glutamate release, and structural remodeling of dendrites. |
| first_indexed | 2024-12-13T08:25:05Z |
| format | Article |
| id | doaj.art-fd759ad3a4ba49b083d5a5cb90a0e7fe |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T08:25:05Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-fd759ad3a4ba49b083d5a5cb90a0e7fe2022-12-21T23:53:54ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-03-011310.3389/fphar.2022.759626759626Acute Ketamine Facilitates Fear Memory Extinction in a Rat Model of PTSD Along With Restoring Glutamatergic Alterations and Dendritic Atrophy in the Prefrontal CortexNathalie Sala0Caterina Paoli1Caterina Paoli2Tiziana Bonifacino3Jessica Mingardi4Emanuele Schiavon5Luca La Via6Marco Milanese7Paolo Tornese8Ashok K. Datusalia9Ashok K. Datusalia10Jessica Rosa11Jessica Rosa12Roberta Facchinetti13Giulia Frumento14Giulia Carini15Floramarida Salerno Scarzella16Caterina Scuderi17Lia Forti18Alessandro Barbon19Giambattista Bonanno20Giambattista Bonanno21Maurizio Popoli22Laura Musazzi23Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmaceutiche, Università Degli Studi di Milano, Milano, ItalyLaboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmaceutiche, Università Degli Studi di Milano, Milano, ItalySchool of Medicine and Surgery, University of Milano-Bicocca, Monza, ItalyDepartment of Pharmacy, Unit of Pharmacology and Toxicology, University of Genoa, Genoa, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, ItalyDepartment of Biotechnology and Life Sciences, University of Insubria, Busto Arsizio, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, ItalyDepartment of Pharmacy, Unit of Pharmacology and Toxicology, University of Genoa, Genoa, ItalyLaboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmaceutiche, Università Degli Studi di Milano, Milano, ItalyLaboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmaceutiche, Università Degli Studi di Milano, Milano, ItalyDepartment of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Raebareli, IndiaLaboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmaceutiche, Università Degli Studi di Milano, Milano, ItalyDepartment of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirao Preto, BrazilDepartment of Physiology and Pharmacology “Vittorio Erspamer”, SAPIENZA University of Rome, Rome, ItalyDepartment of Pharmacy, Unit of Pharmacology and Toxicology, University of Genoa, Genoa, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, ItalyDepartment of Biotechnology and Life Sciences, University of Insubria, Busto Arsizio, ItalyDepartment of Physiology and Pharmacology “Vittorio Erspamer”, SAPIENZA University of Rome, Rome, ItalyDepartment of Biotechnology and Life Sciences, University of Insubria, Busto Arsizio, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, ItalyDepartment of Pharmacy, Unit of Pharmacology and Toxicology, University of Genoa, Genoa, ItalyIRCCS Ospedale Policlinico San Martino, Genoa, ItalyLaboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmaceutiche, Università Degli Studi di Milano, Milano, ItalySchool of Medicine and Surgery, University of Milano-Bicocca, Monza, ItalyStress represents a major risk factor for psychiatric disorders, including post-traumatic stress disorder (PTSD). Recently, we dissected the destabilizing effects of acute stress on the excitatory glutamate system in the prefrontal cortex (PFC). Here, we assessed the effects of single subanesthetic administration of ketamine (10 mg/kg) on glutamate transmission and dendritic arborization in the PFC of footshock (FS)-stressed rats, along with changes in depressive, anxious, and fear extinction behaviors. We found that ketamine, while inducing a mild increase of glutamate release in the PFC of naïve rats, blocked the acute stress-induced enhancement of glutamate release when administered 24 or 72 h before or 6 h after FS. Accordingly, the treatment with ketamine 6 h after FS also reduced the stress-dependent increase of spontaneous excitatory postsynaptic current (sEPSC) amplitude in prelimbic (PL)-PFC. At the same time, ketamine injection 6 h after FS was found to rescue apical dendritic retraction of pyramidal neurons induced by acute stress in PL-PFC and facilitated contextual fear extinction. These results show rapid effects of ketamine in animals subjected to acute FS, in line with previous studies suggesting a therapeutic action of the drug in PTSD models. Our data are consistent with a mechanism of ketamine involving re-establishment of synaptic homeostasis, through restoration of glutamate release, and structural remodeling of dendrites.https://www.frontiersin.org/articles/10.3389/fphar.2022.759626/fullacute stressketaminePTSDprefrontal cortex (PFC)glutamate transmissiondendritic arborization |
| spellingShingle | Nathalie Sala Caterina Paoli Caterina Paoli Tiziana Bonifacino Jessica Mingardi Emanuele Schiavon Luca La Via Marco Milanese Paolo Tornese Ashok K. Datusalia Ashok K. Datusalia Jessica Rosa Jessica Rosa Roberta Facchinetti Giulia Frumento Giulia Carini Floramarida Salerno Scarzella Caterina Scuderi Lia Forti Alessandro Barbon Giambattista Bonanno Giambattista Bonanno Maurizio Popoli Laura Musazzi Acute Ketamine Facilitates Fear Memory Extinction in a Rat Model of PTSD Along With Restoring Glutamatergic Alterations and Dendritic Atrophy in the Prefrontal Cortex Frontiers in Pharmacology acute stress ketamine PTSD prefrontal cortex (PFC) glutamate transmission dendritic arborization |
| title | Acute Ketamine Facilitates Fear Memory Extinction in a Rat Model of PTSD Along With Restoring Glutamatergic Alterations and Dendritic Atrophy in the Prefrontal Cortex |
| title_full | Acute Ketamine Facilitates Fear Memory Extinction in a Rat Model of PTSD Along With Restoring Glutamatergic Alterations and Dendritic Atrophy in the Prefrontal Cortex |
| title_fullStr | Acute Ketamine Facilitates Fear Memory Extinction in a Rat Model of PTSD Along With Restoring Glutamatergic Alterations and Dendritic Atrophy in the Prefrontal Cortex |
| title_full_unstemmed | Acute Ketamine Facilitates Fear Memory Extinction in a Rat Model of PTSD Along With Restoring Glutamatergic Alterations and Dendritic Atrophy in the Prefrontal Cortex |
| title_short | Acute Ketamine Facilitates Fear Memory Extinction in a Rat Model of PTSD Along With Restoring Glutamatergic Alterations and Dendritic Atrophy in the Prefrontal Cortex |
| title_sort | acute ketamine facilitates fear memory extinction in a rat model of ptsd along with restoring glutamatergic alterations and dendritic atrophy in the prefrontal cortex |
| topic | acute stress ketamine PTSD prefrontal cortex (PFC) glutamate transmission dendritic arborization |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.759626/full |
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