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DPCPX, a selective adenosine A1 receptor antagonist, enhances the antidepressant-like effects of imipramine, escitalopram, and reboxetine in mice behavioral tests
The main goal of the present study was to evaluate the influence of the adenosine A1 receptor (A1R) antagonist — DPCPX — on depressive-like behavior in mice, as well as the effect of DPCPX on the activity of imipramine, escitalopram, and reboxetine, each at non-effective doses. The influence of DPCP...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208968/ https://www.ncbi.nlm.nih.gov/pubmed/30094458 http://dx.doi.org/10.1007/s00210-018-1551-z |
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author | Szopa, Aleksandra Poleszak, Ewa Bogatko, Karolina Wyska, Elżbieta Wośko, Sylwia Doboszewska, Urszula Świąder, Katarzyna Wlaź, Aleksandra Dudka, Jarosław Wróbel, Andrzej Wlaź, Piotr Serefko, Anna |
author_facet | Szopa, Aleksandra Poleszak, Ewa Bogatko, Karolina Wyska, Elżbieta Wośko, Sylwia Doboszewska, Urszula Świąder, Katarzyna Wlaź, Aleksandra Dudka, Jarosław Wróbel, Andrzej Wlaź, Piotr Serefko, Anna |
author_sort | Szopa, Aleksandra |
collection | PubMed |
description | The main goal of the present study was to evaluate the influence of the adenosine A1 receptor (A1R) antagonist — DPCPX — on depressive-like behavior in mice, as well as the effect of DPCPX on the activity of imipramine, escitalopram, and reboxetine, each at non-effective doses. The influence of DPCPX on behavior and its influence on the activity of selected antidepressants was evaluated in the forced swim test (FST) and the tail suspension test (TST) in mice. Locomotor activity was measured to verify and exclude false-positive data obtained in the FST and TST. Moreover, serum and brain concentrations of tested antidepressants were determined using HPLC. DPCPX, at doses of 2 and 4 mg/kg, exhibited antidepressant activity in the FST and TST, which was not related to changes in the spontaneous locomotor activity. Co-administration of DPCPX with imipramine, escitalopram, or reboxetine, each at non-active doses, significantly reduced the immobilization period in the FST and TST in mice, which was not due to the increase in locomotor activity. Both antagonists of 5-HT receptors (WAY 100635 and ritanserin) completely antagonized the effect elicited by DPCPX in the behavioral tests. Results of assessment of the nature of the interaction between DPCPX and test drugs show that in the case of DPCPX and imipramine or reboxetine, there were pharmacodynamic interactions, whereas the DPCPX-escitalopram interaction is at least partially pharmacokinetic in nature. Presented outcomes indicate that an inhibition of A1Rs and an increase of monoaminergic transduction in the CNS may offer a novel strategy for the development of antidepressant drugs. |
format | Online Article Text |
id | pubmed-6208968 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-62089682018-11-09 DPCPX, a selective adenosine A1 receptor antagonist, enhances the antidepressant-like effects of imipramine, escitalopram, and reboxetine in mice behavioral tests Szopa, Aleksandra Poleszak, Ewa Bogatko, Karolina Wyska, Elżbieta Wośko, Sylwia Doboszewska, Urszula Świąder, Katarzyna Wlaź, Aleksandra Dudka, Jarosław Wróbel, Andrzej Wlaź, Piotr Serefko, Anna Naunyn Schmiedebergs Arch Pharmacol Original Article The main goal of the present study was to evaluate the influence of the adenosine A1 receptor (A1R) antagonist — DPCPX — on depressive-like behavior in mice, as well as the effect of DPCPX on the activity of imipramine, escitalopram, and reboxetine, each at non-effective doses. The influence of DPCPX on behavior and its influence on the activity of selected antidepressants was evaluated in the forced swim test (FST) and the tail suspension test (TST) in mice. Locomotor activity was measured to verify and exclude false-positive data obtained in the FST and TST. Moreover, serum and brain concentrations of tested antidepressants were determined using HPLC. DPCPX, at doses of 2 and 4 mg/kg, exhibited antidepressant activity in the FST and TST, which was not related to changes in the spontaneous locomotor activity. Co-administration of DPCPX with imipramine, escitalopram, or reboxetine, each at non-active doses, significantly reduced the immobilization period in the FST and TST in mice, which was not due to the increase in locomotor activity. Both antagonists of 5-HT receptors (WAY 100635 and ritanserin) completely antagonized the effect elicited by DPCPX in the behavioral tests. Results of assessment of the nature of the interaction between DPCPX and test drugs show that in the case of DPCPX and imipramine or reboxetine, there were pharmacodynamic interactions, whereas the DPCPX-escitalopram interaction is at least partially pharmacokinetic in nature. Presented outcomes indicate that an inhibition of A1Rs and an increase of monoaminergic transduction in the CNS may offer a novel strategy for the development of antidepressant drugs. Springer Berlin Heidelberg 2018-08-09 2018 /pmc/articles/PMC6208968/ /pubmed/30094458 http://dx.doi.org/10.1007/s00210-018-1551-z Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Article Szopa, Aleksandra Poleszak, Ewa Bogatko, Karolina Wyska, Elżbieta Wośko, Sylwia Doboszewska, Urszula Świąder, Katarzyna Wlaź, Aleksandra Dudka, Jarosław Wróbel, Andrzej Wlaź, Piotr Serefko, Anna DPCPX, a selective adenosine A1 receptor antagonist, enhances the antidepressant-like effects of imipramine, escitalopram, and reboxetine in mice behavioral tests |
title | DPCPX, a selective adenosine A1 receptor antagonist, enhances the antidepressant-like effects of imipramine, escitalopram, and reboxetine in mice behavioral tests |
title_full | DPCPX, a selective adenosine A1 receptor antagonist, enhances the antidepressant-like effects of imipramine, escitalopram, and reboxetine in mice behavioral tests |
title_fullStr | DPCPX, a selective adenosine A1 receptor antagonist, enhances the antidepressant-like effects of imipramine, escitalopram, and reboxetine in mice behavioral tests |
title_full_unstemmed | DPCPX, a selective adenosine A1 receptor antagonist, enhances the antidepressant-like effects of imipramine, escitalopram, and reboxetine in mice behavioral tests |
title_short | DPCPX, a selective adenosine A1 receptor antagonist, enhances the antidepressant-like effects of imipramine, escitalopram, and reboxetine in mice behavioral tests |
title_sort | dpcpx, a selective adenosine a1 receptor antagonist, enhances the antidepressant-like effects of imipramine, escitalopram, and reboxetine in mice behavioral tests |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208968/ https://www.ncbi.nlm.nih.gov/pubmed/30094458 http://dx.doi.org/10.1007/s00210-018-1551-z |
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