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Desensitization of the neuronal 5-HT carrier following its long-term blockade
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Zeitschriftentitel: | The Journal of Neuroscience |
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Personen und Körperschaften: | , , , |
In: | The Journal of Neuroscience, 14, 1994, 5, S. 3036-3047 |
Format: | E-Article |
Sprache: | Englisch |
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Society for Neuroscience
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author_facet |
Pineyro, G Blier, P Dennis, T de Montigny, C Pineyro, G Blier, P Dennis, T de Montigny, C |
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author |
Pineyro, G Blier, P Dennis, T de Montigny, C |
spellingShingle |
Pineyro, G Blier, P Dennis, T de Montigny, C The Journal of Neuroscience Desensitization of the neuronal 5-HT carrier following its long-term blockade General Neuroscience |
author_sort |
pineyro, g |
spelling |
Pineyro, G Blier, P Dennis, T de Montigny, C 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.14-05-03036.1994 <jats:p>In vivo extracellular unitary recordings, in vitro 3H-5-hydroxy- tryptamine (5-HT) uptake, and 3H-paroxetine binding assays were used to assess the effect of acute and long-term administration of the 5-HT reuptake inhibitor paroxetine on the neuronal 5-HT transporter in the rat dorsal hippocampus. Recovery time of the firing activity of CA3 hippocampus pyramidal neurons following microiontophoretic application of 5-HT was used as an index of in vivo reuptake activity. In a first series of experiments, the acute intravenous administration of paroxetine and 5-HT denervation with the neurotoxin 5,7- dihydroxytryptamine produced a marked prolongation of the suppressant effect of 5-HT, indicating that reuptake into 5-HT terminals plays a significant role in terminating the action of microiontophoretically applied 5-HT. In a second series of experiments, rats were treated with paroxetine (10 mg/kg/d, s.c.) for 2 or 21 d. In both treatment groups, there was a marked prolongation of the effect of microiontophoretically applied 5-HT; however, in rats treated for 2 d, the prolongation was significantly greater than that observed in rats treated for 21 d. After the 21 d treatment with paroxetine and a 48 hr washout, the prolongation of the effect of microiontophoretically applied 5-HT by acute intravenous paroxetine was significantly reduced, suggesting a decrease in the number of 5-HT carriers. In keeping with this interpretation, following the same treatment regimen, there was a 50% and 60% reduction of the in vitro 3H-5-HT uptake in hippocampal and dorsal raphe slices, respectively, and a reduced effectiveness of paroxetine in blocking 3H-5-HT uptake in both regions. The determination of the binding parameters of 3H-paroxetine revealed that, in rats treated for 21 d with paroxetine (10 mg/kg/d, s.c.), following a 48 hr washout Kd values were unchanged but Bmax values were reduced by 70% and 60% in hippocampal and cortical membranes, respectively.</jats:p> Desensitization of the neuronal 5-HT carrier following its long-term blockade The Journal of Neuroscience |
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10.1523/jneurosci.14-05-03036.1994 |
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Society for Neuroscience, 1994 |
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1994 |
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Society for Neuroscience |
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series |
The Journal of Neuroscience |
source_id |
49 |
title |
Desensitization of the neuronal 5-HT carrier following its long-term blockade |
title_unstemmed |
Desensitization of the neuronal 5-HT carrier following its long-term blockade |
title_full |
Desensitization of the neuronal 5-HT carrier following its long-term blockade |
title_fullStr |
Desensitization of the neuronal 5-HT carrier following its long-term blockade |
title_full_unstemmed |
Desensitization of the neuronal 5-HT carrier following its long-term blockade |
title_short |
Desensitization of the neuronal 5-HT carrier following its long-term blockade |
title_sort |
desensitization of the neuronal 5-ht carrier following its long-term blockade |
topic |
General Neuroscience |
url |
http://dx.doi.org/10.1523/jneurosci.14-05-03036.1994 |
publishDate |
1994 |
physical |
3036-3047 |
description |
<jats:p>In vivo extracellular unitary recordings, in vitro 3H-5-hydroxy- tryptamine (5-HT) uptake, and 3H-paroxetine binding assays were used to assess the effect of acute and long-term administration of the 5-HT reuptake inhibitor paroxetine on the neuronal 5-HT transporter in the rat dorsal hippocampus. Recovery time of the firing activity of CA3 hippocampus pyramidal neurons following microiontophoretic application of 5-HT was used as an index of in vivo reuptake activity. In a first series of experiments, the acute intravenous administration of paroxetine and 5-HT denervation with the neurotoxin 5,7- dihydroxytryptamine produced a marked prolongation of the suppressant effect of 5-HT, indicating that reuptake into 5-HT terminals plays a significant role in terminating the action of microiontophoretically applied 5-HT. In a second series of experiments, rats were treated with paroxetine (10 mg/kg/d, s.c.) for 2 or 21 d. In both treatment groups, there was a marked prolongation of the effect of microiontophoretically applied 5-HT; however, in rats treated for 2 d, the prolongation was significantly greater than that observed in rats treated for 21 d. After the 21 d treatment with paroxetine and a 48 hr washout, the prolongation of the effect of microiontophoretically applied 5-HT by acute intravenous paroxetine was significantly reduced, suggesting a decrease in the number of 5-HT carriers. In keeping with this interpretation, following the same treatment regimen, there was a 50% and 60% reduction of the in vitro 3H-5-HT uptake in hippocampal and dorsal raphe slices, respectively, and a reduced effectiveness of paroxetine in blocking 3H-5-HT uptake in both regions. The determination of the binding parameters of 3H-paroxetine revealed that, in rats treated for 21 d with paroxetine (10 mg/kg/d, s.c.), following a 48 hr washout Kd values were unchanged but Bmax values were reduced by 70% and 60% in hippocampal and cortical membranes, respectively.</jats:p> |
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author | Pineyro, G, Blier, P, Dennis, T, de Montigny, C |
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author_sort | pineyro, g |
container_issue | 5 |
container_start_page | 3036 |
container_title | The Journal of Neuroscience |
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description | <jats:p>In vivo extracellular unitary recordings, in vitro 3H-5-hydroxy- tryptamine (5-HT) uptake, and 3H-paroxetine binding assays were used to assess the effect of acute and long-term administration of the 5-HT reuptake inhibitor paroxetine on the neuronal 5-HT transporter in the rat dorsal hippocampus. Recovery time of the firing activity of CA3 hippocampus pyramidal neurons following microiontophoretic application of 5-HT was used as an index of in vivo reuptake activity. In a first series of experiments, the acute intravenous administration of paroxetine and 5-HT denervation with the neurotoxin 5,7- dihydroxytryptamine produced a marked prolongation of the suppressant effect of 5-HT, indicating that reuptake into 5-HT terminals plays a significant role in terminating the action of microiontophoretically applied 5-HT. In a second series of experiments, rats were treated with paroxetine (10 mg/kg/d, s.c.) for 2 or 21 d. In both treatment groups, there was a marked prolongation of the effect of microiontophoretically applied 5-HT; however, in rats treated for 2 d, the prolongation was significantly greater than that observed in rats treated for 21 d. After the 21 d treatment with paroxetine and a 48 hr washout, the prolongation of the effect of microiontophoretically applied 5-HT by acute intravenous paroxetine was significantly reduced, suggesting a decrease in the number of 5-HT carriers. In keeping with this interpretation, following the same treatment regimen, there was a 50% and 60% reduction of the in vitro 3H-5-HT uptake in hippocampal and dorsal raphe slices, respectively, and a reduced effectiveness of paroxetine in blocking 3H-5-HT uptake in both regions. The determination of the binding parameters of 3H-paroxetine revealed that, in rats treated for 21 d with paroxetine (10 mg/kg/d, s.c.), following a 48 hr washout Kd values were unchanged but Bmax values were reduced by 70% and 60% in hippocampal and cortical membranes, respectively.</jats:p> |
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spelling | Pineyro, G Blier, P Dennis, T de Montigny, C 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.14-05-03036.1994 <jats:p>In vivo extracellular unitary recordings, in vitro 3H-5-hydroxy- tryptamine (5-HT) uptake, and 3H-paroxetine binding assays were used to assess the effect of acute and long-term administration of the 5-HT reuptake inhibitor paroxetine on the neuronal 5-HT transporter in the rat dorsal hippocampus. Recovery time of the firing activity of CA3 hippocampus pyramidal neurons following microiontophoretic application of 5-HT was used as an index of in vivo reuptake activity. In a first series of experiments, the acute intravenous administration of paroxetine and 5-HT denervation with the neurotoxin 5,7- dihydroxytryptamine produced a marked prolongation of the suppressant effect of 5-HT, indicating that reuptake into 5-HT terminals plays a significant role in terminating the action of microiontophoretically applied 5-HT. In a second series of experiments, rats were treated with paroxetine (10 mg/kg/d, s.c.) for 2 or 21 d. In both treatment groups, there was a marked prolongation of the effect of microiontophoretically applied 5-HT; however, in rats treated for 2 d, the prolongation was significantly greater than that observed in rats treated for 21 d. After the 21 d treatment with paroxetine and a 48 hr washout, the prolongation of the effect of microiontophoretically applied 5-HT by acute intravenous paroxetine was significantly reduced, suggesting a decrease in the number of 5-HT carriers. In keeping with this interpretation, following the same treatment regimen, there was a 50% and 60% reduction of the in vitro 3H-5-HT uptake in hippocampal and dorsal raphe slices, respectively, and a reduced effectiveness of paroxetine in blocking 3H-5-HT uptake in both regions. The determination of the binding parameters of 3H-paroxetine revealed that, in rats treated for 21 d with paroxetine (10 mg/kg/d, s.c.), following a 48 hr washout Kd values were unchanged but Bmax values were reduced by 70% and 60% in hippocampal and cortical membranes, respectively.</jats:p> Desensitization of the neuronal 5-HT carrier following its long-term blockade The Journal of Neuroscience |
spellingShingle | Pineyro, G, Blier, P, Dennis, T, de Montigny, C, The Journal of Neuroscience, Desensitization of the neuronal 5-HT carrier following its long-term blockade, General Neuroscience |
title | Desensitization of the neuronal 5-HT carrier following its long-term blockade |
title_full | Desensitization of the neuronal 5-HT carrier following its long-term blockade |
title_fullStr | Desensitization of the neuronal 5-HT carrier following its long-term blockade |
title_full_unstemmed | Desensitization of the neuronal 5-HT carrier following its long-term blockade |
title_short | Desensitization of the neuronal 5-HT carrier following its long-term blockade |
title_sort | desensitization of the neuronal 5-ht carrier following its long-term blockade |
title_unstemmed | Desensitization of the neuronal 5-HT carrier following its long-term blockade |
topic | General Neuroscience |
url | http://dx.doi.org/10.1523/jneurosci.14-05-03036.1994 |