Pharmacodynamics of the Glutamate Receptor Antagonists in the Rat Barrel Cortex
Epipial application is one of the approaches for drug delivery into the cortex. However, passive diffusion of epipially applied drugs through the cortical depth may be slow, and different drug concentrations may be achieved at different rates across the cortical depth. Here, we explored the pharmaco...
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Frontiers Media S.A.
2018-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.00698/full |
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| author | Daria Vinokurova Daria Vinokurova Andrey V. Zakharov Julia Lebedeva Gulshat F. Burkhanova Kseniya A. Chernova Nailya Lotfullina Nailya Lotfullina Rustem Khazipov Rustem Khazipov Guzel Valeeva |
| author_facet | Daria Vinokurova Daria Vinokurova Andrey V. Zakharov Julia Lebedeva Gulshat F. Burkhanova Kseniya A. Chernova Nailya Lotfullina Nailya Lotfullina Rustem Khazipov Rustem Khazipov Guzel Valeeva |
| author_sort | Daria Vinokurova |
| collection | DOAJ |
| description | Epipial application is one of the approaches for drug delivery into the cortex. However, passive diffusion of epipially applied drugs through the cortical depth may be slow, and different drug concentrations may be achieved at different rates across the cortical depth. Here, we explored the pharmacodynamics of the inhibitory effects of epipially applied ionotropic glutamate receptor antagonists CNQX and dAPV on sensory-evoked and spontaneous activity across layers of the cortical barrel column in urethane-anesthetized rats. The inhibitory effects of CNQX and dAPV were observed at concentrations that were an order higher than in slices in vitro, and they slowly developed from the cortical surface to depth after epipial application. The level of the inhibitory effects also followed the surface-to-depth gradient, with full inhibition of sensory evoked potentials (SEPs) in the supragranular layers and L4 and only partial inhibition in L5 and L6. During epipial CNQX and dAPV application, spontaneous activity and the late component of multiple unit activity (MUA) during sensory-evoked responses were suppressed faster than the short-latency MUA component. Despite complete suppression of SEPs in L4, sensory-evoked short-latency multiunit responses in L4 persisted, and they were suppressed by further addition of lidocaine suggesting that spikes in thalamocortical axons contribute ∼20% to early multiunit responses. Epipial CNQX and dAPV also completely suppressed sensory-evoked very fast (∼500 Hz) oscillations and spontaneous slow wave activity in L2/3 and L4. However, delta oscillations persisted in L5/6. Thus, CNQX and dAPV exert inhibitory actions on cortical activity during epipial application at much higher concentrations than in vitro, and the pharmacodynamics of their inhibitory effects is characterized by the surface-to-depth gradients in the rate of development and the level of inhibition of sensory-evoked and spontaneous cortical activity. |
| first_indexed | 2024-12-11T19:31:23Z |
| format | Article |
| id | doaj.art-12235c99e8984acd803d10bfa6e326e4 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-11T19:31:23Z |
| publishDate | 2018-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-12235c99e8984acd803d10bfa6e326e42022-12-22T00:53:15ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-07-01910.3389/fphar.2018.00698380594Pharmacodynamics of the Glutamate Receptor Antagonists in the Rat Barrel CortexDaria Vinokurova0Daria Vinokurova1Andrey V. Zakharov2Julia Lebedeva3Gulshat F. Burkhanova4Kseniya A. Chernova5Nailya Lotfullina6Nailya Lotfullina7Rustem Khazipov8Rustem Khazipov9Guzel Valeeva10Laboratory of Neurobiology, Kazan Federal University, Kazan, RussiaMediterranean Institute of Neurobiology – National Institute of Health and Medical Research, Aix-Marseille University, UMR1249, Marseille, FranceLaboratory of Neurobiology, Kazan Federal University, Kazan, RussiaLaboratory of Neurobiology, Kazan Federal University, Kazan, RussiaLaboratory of Neurobiology, Kazan Federal University, Kazan, RussiaLaboratory of Neurobiology, Kazan Federal University, Kazan, RussiaLaboratory of Neurobiology, Kazan Federal University, Kazan, RussiaMediterranean Institute of Neurobiology – National Institute of Health and Medical Research, Aix-Marseille University, UMR1249, Marseille, FranceLaboratory of Neurobiology, Kazan Federal University, Kazan, RussiaMediterranean Institute of Neurobiology – National Institute of Health and Medical Research, Aix-Marseille University, UMR1249, Marseille, FranceLaboratory of Neurobiology, Kazan Federal University, Kazan, RussiaEpipial application is one of the approaches for drug delivery into the cortex. However, passive diffusion of epipially applied drugs through the cortical depth may be slow, and different drug concentrations may be achieved at different rates across the cortical depth. Here, we explored the pharmacodynamics of the inhibitory effects of epipially applied ionotropic glutamate receptor antagonists CNQX and dAPV on sensory-evoked and spontaneous activity across layers of the cortical barrel column in urethane-anesthetized rats. The inhibitory effects of CNQX and dAPV were observed at concentrations that were an order higher than in slices in vitro, and they slowly developed from the cortical surface to depth after epipial application. The level of the inhibitory effects also followed the surface-to-depth gradient, with full inhibition of sensory evoked potentials (SEPs) in the supragranular layers and L4 and only partial inhibition in L5 and L6. During epipial CNQX and dAPV application, spontaneous activity and the late component of multiple unit activity (MUA) during sensory-evoked responses were suppressed faster than the short-latency MUA component. Despite complete suppression of SEPs in L4, sensory-evoked short-latency multiunit responses in L4 persisted, and they were suppressed by further addition of lidocaine suggesting that spikes in thalamocortical axons contribute ∼20% to early multiunit responses. Epipial CNQX and dAPV also completely suppressed sensory-evoked very fast (∼500 Hz) oscillations and spontaneous slow wave activity in L2/3 and L4. However, delta oscillations persisted in L5/6. Thus, CNQX and dAPV exert inhibitory actions on cortical activity during epipial application at much higher concentrations than in vitro, and the pharmacodynamics of their inhibitory effects is characterized by the surface-to-depth gradients in the rate of development and the level of inhibition of sensory-evoked and spontaneous cortical activity.https://www.frontiersin.org/article/10.3389/fphar.2018.00698/fullglutamate receptor antagonistsbarrel cortexepipial applicationdrug deliverysensory-evoked potentialfast oscillations |
| spellingShingle | Daria Vinokurova Daria Vinokurova Andrey V. Zakharov Julia Lebedeva Gulshat F. Burkhanova Kseniya A. Chernova Nailya Lotfullina Nailya Lotfullina Rustem Khazipov Rustem Khazipov Guzel Valeeva Pharmacodynamics of the Glutamate Receptor Antagonists in the Rat Barrel Cortex Frontiers in Pharmacology glutamate receptor antagonists barrel cortex epipial application drug delivery sensory-evoked potential fast oscillations |
| title | Pharmacodynamics of the Glutamate Receptor Antagonists in the Rat Barrel Cortex |
| title_full | Pharmacodynamics of the Glutamate Receptor Antagonists in the Rat Barrel Cortex |
| title_fullStr | Pharmacodynamics of the Glutamate Receptor Antagonists in the Rat Barrel Cortex |
| title_full_unstemmed | Pharmacodynamics of the Glutamate Receptor Antagonists in the Rat Barrel Cortex |
| title_short | Pharmacodynamics of the Glutamate Receptor Antagonists in the Rat Barrel Cortex |
| title_sort | pharmacodynamics of the glutamate receptor antagonists in the rat barrel cortex |
| topic | glutamate receptor antagonists barrel cortex epipial application drug delivery sensory-evoked potential fast oscillations |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.00698/full |
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