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Impact of subanesthetic doses of ketamine on AMPA-mediated responses in rats: An in vivo electrophysiological study on monoaminergic and glutamatergic neurons
The rapid antidepressant action of a subanesthetic dose of ketamine in treatment-resistant patients represents the most striking recent breakthrough in the understanding of the antidepressant response. Evidence demonstrates tight interactions between the glutamatergic and monoaminergic systems. It i...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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SAGE Publications
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469544/ https://www.ncbi.nlm.nih.gov/pubmed/25759403 http://dx.doi.org/10.1177/0269881115573809 |
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author | El Iskandrani, Kareem S Oosterhof, Chris A El Mansari, Mostafa Blier, Pierre |
author_facet | El Iskandrani, Kareem S Oosterhof, Chris A El Mansari, Mostafa Blier, Pierre |
author_sort | El Iskandrani, Kareem S |
collection | PubMed |
description | The rapid antidepressant action of a subanesthetic dose of ketamine in treatment-resistant patients represents the most striking recent breakthrough in the understanding of the antidepressant response. Evidence demonstrates tight interactions between the glutamatergic and monoaminergic systems. It is thus hypothesized that monoamine systems may play a role in the immediate/rapid effects of ketamine. In vivo electrophysiological recordings were carried in male rats following ketamine administration (10 and 25 mg/kg, i.p.) to first assess its effects on monoaminergic neuron firing. In a second series of experiments, the effects of ketamine administration on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- and N-methyl-D-aspartate receptor (NMDA)-evoked responses in hippocampus CA3 pyramidal neurons were also investigated using micro-iontophoretic applications. Although acute (~2 hours) ketamine administration did not affect the mean firing activity of dorsal raphe serotonin and ventral tegmental area dopamine neurons, it did increase that of locus coeruleus norepinephrine neurons. In the latter brain region, while ketamine also enhanced bursting activity, it did increase population activity of dopamine neurons in the ventral tegmental area. These effects of ketamine were prevented by the prior administration of the AMPA receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide. An increase in AMPA-evoked response of CA3 pyramidal neurons was also observed 30 minutes following acute ketamine administration. The present findings suggest that acute ketamine administration produces a rapid enhancement of catecholaminergic neurons firing activity through an amplification of AMPA transmission. These effects may play a crucial role in the antidepressant effects of ketamine observed shortly following its infusion in depressed patients. |
format | Online Article Text |
id | pubmed-4469544 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-44695442015-06-30 Impact of subanesthetic doses of ketamine on AMPA-mediated responses in rats: An in vivo electrophysiological study on monoaminergic and glutamatergic neurons El Iskandrani, Kareem S Oosterhof, Chris A El Mansari, Mostafa Blier, Pierre J Psychopharmacol Original Papers The rapid antidepressant action of a subanesthetic dose of ketamine in treatment-resistant patients represents the most striking recent breakthrough in the understanding of the antidepressant response. Evidence demonstrates tight interactions between the glutamatergic and monoaminergic systems. It is thus hypothesized that monoamine systems may play a role in the immediate/rapid effects of ketamine. In vivo electrophysiological recordings were carried in male rats following ketamine administration (10 and 25 mg/kg, i.p.) to first assess its effects on monoaminergic neuron firing. In a second series of experiments, the effects of ketamine administration on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- and N-methyl-D-aspartate receptor (NMDA)-evoked responses in hippocampus CA3 pyramidal neurons were also investigated using micro-iontophoretic applications. Although acute (~2 hours) ketamine administration did not affect the mean firing activity of dorsal raphe serotonin and ventral tegmental area dopamine neurons, it did increase that of locus coeruleus norepinephrine neurons. In the latter brain region, while ketamine also enhanced bursting activity, it did increase population activity of dopamine neurons in the ventral tegmental area. These effects of ketamine were prevented by the prior administration of the AMPA receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide. An increase in AMPA-evoked response of CA3 pyramidal neurons was also observed 30 minutes following acute ketamine administration. The present findings suggest that acute ketamine administration produces a rapid enhancement of catecholaminergic neurons firing activity through an amplification of AMPA transmission. These effects may play a crucial role in the antidepressant effects of ketamine observed shortly following its infusion in depressed patients. SAGE Publications 2015-07 /pmc/articles/PMC4469544/ /pubmed/25759403 http://dx.doi.org/10.1177/0269881115573809 Text en © The Author(s) 2015 http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution 3.0 License (http://www.creativecommons.org/licenses/by/3.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (http://www.uk.sagepub.com/aboutus/openaccess.htm). |
spellingShingle | Original Papers El Iskandrani, Kareem S Oosterhof, Chris A El Mansari, Mostafa Blier, Pierre Impact of subanesthetic doses of ketamine on AMPA-mediated responses in rats: An in vivo electrophysiological study on monoaminergic and glutamatergic neurons |
title | Impact of subanesthetic doses of ketamine on AMPA-mediated responses in rats: An in vivo electrophysiological study on monoaminergic and glutamatergic neurons |
title_full | Impact of subanesthetic doses of ketamine on AMPA-mediated responses in rats: An in vivo electrophysiological study on monoaminergic and glutamatergic neurons |
title_fullStr | Impact of subanesthetic doses of ketamine on AMPA-mediated responses in rats: An in vivo electrophysiological study on monoaminergic and glutamatergic neurons |
title_full_unstemmed | Impact of subanesthetic doses of ketamine on AMPA-mediated responses in rats: An in vivo electrophysiological study on monoaminergic and glutamatergic neurons |
title_short | Impact of subanesthetic doses of ketamine on AMPA-mediated responses in rats: An in vivo electrophysiological study on monoaminergic and glutamatergic neurons |
title_sort | impact of subanesthetic doses of ketamine on ampa-mediated responses in rats: an in vivo electrophysiological study on monoaminergic and glutamatergic neurons |
topic | Original Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469544/ https://www.ncbi.nlm.nih.gov/pubmed/25759403 http://dx.doi.org/10.1177/0269881115573809 |
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