R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity.
Modafinil is a wake promoting drug approved for clinical use and also has cognitive enhancing properties. Its enantiomer R-Modafinil (R-MO) is not well studied in regard to cognitive enhancing properties. Hence we studied its effect in a spatial memory paradigm and its possible effects on dentate gy...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5482457?pdf=render |
| _version_ | 1819113545702309888 |
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| author | Bharanidharan Shanmugasundaram Yogesh D Aher Jana Aradska Marija Ilic Daniel Daba Feyissa Predrag Kalaba Nilima Y Aher Vladimir Dragacevic Babak Saber Marouf Thierry Langer Harald H Sitte Harald Hoeger Gert Lubec Volker Korz |
| author_facet | Bharanidharan Shanmugasundaram Yogesh D Aher Jana Aradska Marija Ilic Daniel Daba Feyissa Predrag Kalaba Nilima Y Aher Vladimir Dragacevic Babak Saber Marouf Thierry Langer Harald H Sitte Harald Hoeger Gert Lubec Volker Korz |
| author_sort | Bharanidharan Shanmugasundaram |
| collection | DOAJ |
| description | Modafinil is a wake promoting drug approved for clinical use and also has cognitive enhancing properties. Its enantiomer R-Modafinil (R-MO) is not well studied in regard to cognitive enhancing properties. Hence we studied its effect in a spatial memory paradigm and its possible effects on dentate gyrus long-term potentiation (DG-LTP). Clinically relevant doses of R-MO, vehicle dimethyl sulfoxide (DMSO) or saline were administered for three days during the hole-board test and in in vivo DG-LTP. Synaptic levels of dopamine receptors D1R, D2R, dopamine transporter (DAT), and its phosphorylated form (ph-DAT) in DG tissue 4 h after LTP induction were quantified by western blot analysis. Monoamine reuptake and release assays were performed by using transfected HEK-293 cells. Possible neurotoxic side effects on general behaviour were also studied. R-MO at both doses significantly enhanced spatial reference memory during the last training session and during memory retrieval compared to DMSO vehicle but not when compared to saline treated rats. Similarly, R-MO rescues DG-LTP from impairing effects of DMSO. DMSO reduced memory performance and LTP magnitude when compared to saline treated groups. The synaptic DR1 levels in R-MO groups were significantly decreased compared to DMSO group but were comparable with saline treated animals. We found no effect of R-MO in neurotoxicity tests. Thus, our results support the notion that LTP-like synaptic plasticity processes could be one of the factors contributing to the cognitive enhancing effects of spatial memory traces. D1R may play an important regulatory role in these processes. |
| first_indexed | 2024-12-22T04:31:07Z |
| format | Article |
| id | doaj.art-06c0c33a6b25495b9e313ce80680a0eb |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T04:31:07Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-06c0c33a6b25495b9e313ce80680a0eb2022-12-21T18:39:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01126e017967510.1371/journal.pone.0179675R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity.Bharanidharan ShanmugasundaramYogesh D AherJana AradskaMarija IlicDaniel Daba FeyissaPredrag KalabaNilima Y AherVladimir DragacevicBabak Saber MaroufThierry LangerHarald H SitteHarald HoegerGert LubecVolker KorzModafinil is a wake promoting drug approved for clinical use and also has cognitive enhancing properties. Its enantiomer R-Modafinil (R-MO) is not well studied in regard to cognitive enhancing properties. Hence we studied its effect in a spatial memory paradigm and its possible effects on dentate gyrus long-term potentiation (DG-LTP). Clinically relevant doses of R-MO, vehicle dimethyl sulfoxide (DMSO) or saline were administered for three days during the hole-board test and in in vivo DG-LTP. Synaptic levels of dopamine receptors D1R, D2R, dopamine transporter (DAT), and its phosphorylated form (ph-DAT) in DG tissue 4 h after LTP induction were quantified by western blot analysis. Monoamine reuptake and release assays were performed by using transfected HEK-293 cells. Possible neurotoxic side effects on general behaviour were also studied. R-MO at both doses significantly enhanced spatial reference memory during the last training session and during memory retrieval compared to DMSO vehicle but not when compared to saline treated rats. Similarly, R-MO rescues DG-LTP from impairing effects of DMSO. DMSO reduced memory performance and LTP magnitude when compared to saline treated groups. The synaptic DR1 levels in R-MO groups were significantly decreased compared to DMSO group but were comparable with saline treated animals. We found no effect of R-MO in neurotoxicity tests. Thus, our results support the notion that LTP-like synaptic plasticity processes could be one of the factors contributing to the cognitive enhancing effects of spatial memory traces. D1R may play an important regulatory role in these processes.http://europepmc.org/articles/PMC5482457?pdf=render |
| spellingShingle | Bharanidharan Shanmugasundaram Yogesh D Aher Jana Aradska Marija Ilic Daniel Daba Feyissa Predrag Kalaba Nilima Y Aher Vladimir Dragacevic Babak Saber Marouf Thierry Langer Harald H Sitte Harald Hoeger Gert Lubec Volker Korz R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity. PLoS ONE |
| title | R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity. |
| title_full | R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity. |
| title_fullStr | R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity. |
| title_full_unstemmed | R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity. |
| title_short | R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity. |
| title_sort | r modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity |
| url | http://europepmc.org/articles/PMC5482457?pdf=render |
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