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...
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MDPI AG
2021-07-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/7/1007 |
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| author | Martina Janikova Karolina Mainerova Iveta Vojtechova Tomas Petrasek Jan Svoboda Ales Stuchlik |
| author_facet | Martina Janikova Karolina Mainerova Iveta Vojtechova Tomas Petrasek Jan Svoboda Ales Stuchlik |
| author_sort | Martina Janikova |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T09:45:11Z |
| format | Article |
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| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T09:45:11Z |
| publishDate | 2021-07-01 |
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| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-9343b94ace68434a8cfc318b1be5711d2023-11-22T03:18:39ZengMDPI AGBiomolecules2218-273X2021-07-01117100710.3390/biom11071007Memantine and Riluzole Exacerbate, Rather Than Ameliorate Behavioral Deficits Induced by 8-OH-DPAT Sensitization in a Spatial TaskMartina Janikova0Karolina Mainerova1Iveta Vojtechova2Tomas Petrasek3Jan Svoboda4Ales Stuchlik5Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicChronic 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.https://www.mdpi.com/2218-273X/11/7/1007obsessive-compulsive disorder8-OH-DPATmemantineriluzolespatial learningmemory |
| spellingShingle | Martina Janikova Karolina Mainerova Iveta Vojtechova Tomas Petrasek Jan Svoboda Ales Stuchlik Memantine and Riluzole Exacerbate, Rather Than Ameliorate Behavioral Deficits Induced by 8-OH-DPAT Sensitization in a Spatial Task Biomolecules obsessive-compulsive disorder 8-OH-DPAT memantine riluzole spatial learning memory |
| 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 | obsessive-compulsive disorder 8-OH-DPAT memantine riluzole spatial learning memory |
| url | https://www.mdpi.com/2218-273X/11/7/1007 |
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