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Memantine and Riluzole Exacerbate, Rather Than Ameliorate Behavioral Deficits Induced by 8-OH-DPAT Sensitization in a Spatial Task
Chronic sensitization to serotonin 1A and 7 receptors agonist 8-OH-DPAT induces compulsive checking and perseverative behavior. As such, it has been used to model obsessive-compulsive disorder (OCD)-like behavior in mice and rats. In this study, we tested spatial learning in the 8-OH-DPAT model of O...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301967/ https://www.ncbi.nlm.nih.gov/pubmed/34356631 http://dx.doi.org/10.3390/biom11071007 |
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author | Janikova, Martina Mainerova, Karolina Vojtechova, Iveta Petrasek, Tomas Svoboda, Jan Stuchlik, Ales |
author_facet | Janikova, Martina Mainerova, Karolina Vojtechova, Iveta Petrasek, Tomas Svoboda, Jan Stuchlik, Ales |
author_sort | Janikova, Martina |
collection | PubMed |
description | Chronic sensitization to serotonin 1A and 7 receptors agonist 8-OH-DPAT induces compulsive checking and perseverative behavior. As such, it has been used to model obsessive-compulsive disorder (OCD)-like behavior in mice and rats. In this study, we tested spatial learning in the 8-OH-DPAT model of OCD and the effect of co-administration of memantine and riluzole—glutamate-modulating agents that have been shown to be effective in several clinical trials. Rats were tested in the active place avoidance task in the Carousel maze, where they learned to avoid the visually imperceptible shock sector. All rats were subcutaneously injected with 8-OH-DPAT (0.25 mg/kg) or saline (control group) during habituation. During acquisition, they were pretreated with riluzole (1 mg/kg), memantine (1 mg/kg), or saline solution 30 min before each session and injected with 8-OH-DPAT (“OH” groups) or saline (“saline” groups) right before the experiment. We found that repeated application of 8-OH-DPAT during both habituation and acquisition significantly increased locomotion, but it impaired the ability to avoid the shock sector. However, the application of 8-OH-DPAT in habituation had no impact on the learning process if discontinued in acquisition. Similarly, memantine and riluzole did not affect the measured parameters in the “saline” groups, but in the “OH” groups, they significantly increased locomotion. In addition, riluzole increased the number of entrances and decreased the maximum time avoided of the shock sector. We conclude that monotherapy with glutamate-modulating agents does not reduce but exacerbates cognitive symptoms in the animal model of OCD. |
format | Online Article Text |
id | pubmed-8301967 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83019672021-07-24 Memantine and Riluzole Exacerbate, Rather Than Ameliorate Behavioral Deficits Induced by 8-OH-DPAT Sensitization in a Spatial Task Janikova, Martina Mainerova, Karolina Vojtechova, Iveta Petrasek, Tomas Svoboda, Jan Stuchlik, Ales Biomolecules Article Chronic sensitization to serotonin 1A and 7 receptors agonist 8-OH-DPAT induces compulsive checking and perseverative behavior. As such, it has been used to model obsessive-compulsive disorder (OCD)-like behavior in mice and rats. In this study, we tested spatial learning in the 8-OH-DPAT model of OCD and the effect of co-administration of memantine and riluzole—glutamate-modulating agents that have been shown to be effective in several clinical trials. Rats were tested in the active place avoidance task in the Carousel maze, where they learned to avoid the visually imperceptible shock sector. All rats were subcutaneously injected with 8-OH-DPAT (0.25 mg/kg) or saline (control group) during habituation. During acquisition, they were pretreated with riluzole (1 mg/kg), memantine (1 mg/kg), or saline solution 30 min before each session and injected with 8-OH-DPAT (“OH” groups) or saline (“saline” groups) right before the experiment. We found that repeated application of 8-OH-DPAT during both habituation and acquisition significantly increased locomotion, but it impaired the ability to avoid the shock sector. However, the application of 8-OH-DPAT in habituation had no impact on the learning process if discontinued in acquisition. Similarly, memantine and riluzole did not affect the measured parameters in the “saline” groups, but in the “OH” groups, they significantly increased locomotion. In addition, riluzole increased the number of entrances and decreased the maximum time avoided of the shock sector. We conclude that monotherapy with glutamate-modulating agents does not reduce but exacerbates cognitive symptoms in the animal model of OCD. MDPI 2021-07-09 /pmc/articles/PMC8301967/ /pubmed/34356631 http://dx.doi.org/10.3390/biom11071007 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Janikova, Martina Mainerova, Karolina Vojtechova, Iveta Petrasek, Tomas Svoboda, Jan Stuchlik, Ales Memantine and Riluzole Exacerbate, Rather Than Ameliorate Behavioral Deficits Induced by 8-OH-DPAT Sensitization in a Spatial Task |
title | Memantine and Riluzole Exacerbate, Rather Than Ameliorate Behavioral Deficits Induced by 8-OH-DPAT Sensitization in a Spatial Task |
title_full | Memantine and Riluzole Exacerbate, Rather Than Ameliorate Behavioral Deficits Induced by 8-OH-DPAT Sensitization in a Spatial Task |
title_fullStr | Memantine and Riluzole Exacerbate, Rather Than Ameliorate Behavioral Deficits Induced by 8-OH-DPAT Sensitization in a Spatial Task |
title_full_unstemmed | Memantine and Riluzole Exacerbate, Rather Than Ameliorate Behavioral Deficits Induced by 8-OH-DPAT Sensitization in a Spatial Task |
title_short | Memantine and Riluzole Exacerbate, Rather Than Ameliorate Behavioral Deficits Induced by 8-OH-DPAT Sensitization in a Spatial Task |
title_sort | memantine and riluzole exacerbate, rather than ameliorate behavioral deficits induced by 8-oh-dpat sensitization in a spatial task |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301967/ https://www.ncbi.nlm.nih.gov/pubmed/34356631 http://dx.doi.org/10.3390/biom11071007 |
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