Differences between ketamine’s short-term and long-term effects on brain circuitry in depression
| Autor: | Markus Sack, Jonathan Rochus Reinwald, Alexander Sartorius, Robert Becker, Barbara Vollmayr, Alejandro Cosa-Linan, Natalia Gass, Wolfgang Weber-Fahr |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine medicine.drug_class Hippocampal formation Dissociative Hippocampus Article lcsh:RC321-571 Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Thalamus Connectome Animals Medicine Ketamine Cerebrum lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Biological Psychiatry Cerebral Cortex Habenula Behavior Animal medicine.diagnostic_test Depression business.industry Cognitive flexibility Cognition Magnetic Resonance Imaging Antidepressive Agents Rats Disease Models Animal Psychiatry and Mental health 030104 developmental biology Antidepressant Nerve Net business Functional magnetic resonance imaging Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Translational Psychiatry, Vol 9, Iss 1, Pp 1-11 (2019) Translational Psychiatry |
| ISSN: | 2158-3188 |
| Popis: | Ketamine acts as a rapid clinical antidepressant at 25 min after injection with effects sustained for 7 days. As dissociative effects emerging acutely after injection are not entirely discernible from therapeutic action, we aimed to dissect the differences between short-term and long-term response to ketamine to elucidate potential imaging biomarkers of ketamine’s antidepressant effect. We used a genetical model of depression, in which we bred depressed negative cognitive state (NC) and non-depressed positive cognitive state (PC) rat strains. Four parallel rat groups underwent stress-escape testing and a week later received either S-ketamine (12 NC, 13 PC) or saline (12 NC, 12 PC). We acquired resting-state functional magnetic resonance imaging time series before injection and at 30 min and 48 h after injection. Graph analysis was used to calculate brain network properties. We identified ketamine’s distinct action over time in a qualitative manner. The rapid response entailed robust and strain-independent topological modifications in cognitive, sensory, emotion, and reward-related circuitry, including regions that exhibited correlation of connectivity metrics with depressive behavior, and which could explain ketamine’s dissociative and antidepressant properties. At 48 h ketamine had mainly strain-specific action normalizing habenula, midline thalamus, and hippocampal connectivity measures in depressed rats. As these nodes mediate cognitive flexibility impaired in depression, action within this circuitry presumably reflects ketamine’s procognitive effects induced only in depressed patients. This finding is especially valid, as our model represents cognitive aspects of depression. These empirically defined circuits explain ketamine’s distinct action over time and might serve as translational imaging correlates of antidepressant response in preclinical testing. |
| Databáze: | OpenAIRE |
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