Cargando…
The Requirement of L-Type Voltage-Dependent Calcium Channel (L-VDCC) in the Rapid-Acting Antidepressant-Like Effects of Scopolamine in Mice
BACKGROUND: Previous studies have shown that a low dose of scopolamine produces rapid-acting antidepressant-like actions in rodents. Understanding the mechanisms underlying this effect and the dose-dependent variations of drug responses remains an important task. L-type voltage-dependent calcium cha...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793820/ https://www.ncbi.nlm.nih.gov/pubmed/29020410 http://dx.doi.org/10.1093/ijnp/pyx080 |
_version_ | 1783297027885498368 |
---|---|
author | Yu, Hanjie Li, Mengmeng Shen, Xinbei Lv, Dan Sun, Xin Wang, Jinting Gu, Xinmei Hu, Jingning Wang, Chuang |
author_facet | Yu, Hanjie Li, Mengmeng Shen, Xinbei Lv, Dan Sun, Xin Wang, Jinting Gu, Xinmei Hu, Jingning Wang, Chuang |
author_sort | Yu, Hanjie |
collection | PubMed |
description | BACKGROUND: Previous studies have shown that a low dose of scopolamine produces rapid-acting antidepressant-like actions in rodents. Understanding the mechanisms underlying this effect and the dose-dependent variations of drug responses remains an important task. L-type voltage-dependent calcium channels were found to mediate rapid-acting antidepressant effects of certain medications (e.g., ketamine). Therefore, it is of great interest to determine the involvement of L-type voltage-dependent calcium channels in the action of scopolamine. METHODS: Herein, we investigated the mechanisms underlying behavioral responses to various doses of scopolamine in mice to clarify the involvement of L-type voltage-dependent calcium channels in its modes of action. Open field test, novel object recognition test, and forced swimming test were performed on mice administered varied doses of scopolamine (0.025, 0.05, 0.1, 1, and 3 mg/kg, i.p.) alone or combined with L-type voltage-dependent calcium channel blocker verapamil (5 mg/kg, i.p.). Then, the changes in brain-derived neurotrophic factor and neuropeptide VGF (nonacronymic) levels in the hippocampus and prefrontal cortex of these mice were analyzed. RESULTS: Low doses of scopolamine (0.025 and 0.05 mg/kg) produced significant antidepressant-like effects in the forced swimming test, while higher doses (1 and 3 mg/kg) resulted in significant memory deficits and depressive-like behaviors. Moreover, the behavioral changes in responses to various doses may be related to the upregulation (0.025 and 0.05 mg/kg) and downregulation (1 and 3 mg/kg) of brain-derived neurotrophic factor and VGF in the hippocampus and prefrontal cortex in mice. We further found that the rapid-acting antidepressant-like effects and the upregulation on brain-derived neurotrophic factor and VGF produced by a low dose of scopolamine (0.025 mg/kg) were completely blocked by verapamil. CONCLUSIONS: These results indicate that L-type voltage-dependent calcium channels are likely involved in the behavioral changes in response to various doses of scopolamine through the regulation of brain-derived neurotrophic factor and VGF levels. |
format | Online Article Text |
id | pubmed-5793820 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57938202018-02-06 The Requirement of L-Type Voltage-Dependent Calcium Channel (L-VDCC) in the Rapid-Acting Antidepressant-Like Effects of Scopolamine in Mice Yu, Hanjie Li, Mengmeng Shen, Xinbei Lv, Dan Sun, Xin Wang, Jinting Gu, Xinmei Hu, Jingning Wang, Chuang Int J Neuropsychopharmacol Regular Research Articles BACKGROUND: Previous studies have shown that a low dose of scopolamine produces rapid-acting antidepressant-like actions in rodents. Understanding the mechanisms underlying this effect and the dose-dependent variations of drug responses remains an important task. L-type voltage-dependent calcium channels were found to mediate rapid-acting antidepressant effects of certain medications (e.g., ketamine). Therefore, it is of great interest to determine the involvement of L-type voltage-dependent calcium channels in the action of scopolamine. METHODS: Herein, we investigated the mechanisms underlying behavioral responses to various doses of scopolamine in mice to clarify the involvement of L-type voltage-dependent calcium channels in its modes of action. Open field test, novel object recognition test, and forced swimming test were performed on mice administered varied doses of scopolamine (0.025, 0.05, 0.1, 1, and 3 mg/kg, i.p.) alone or combined with L-type voltage-dependent calcium channel blocker verapamil (5 mg/kg, i.p.). Then, the changes in brain-derived neurotrophic factor and neuropeptide VGF (nonacronymic) levels in the hippocampus and prefrontal cortex of these mice were analyzed. RESULTS: Low doses of scopolamine (0.025 and 0.05 mg/kg) produced significant antidepressant-like effects in the forced swimming test, while higher doses (1 and 3 mg/kg) resulted in significant memory deficits and depressive-like behaviors. Moreover, the behavioral changes in responses to various doses may be related to the upregulation (0.025 and 0.05 mg/kg) and downregulation (1 and 3 mg/kg) of brain-derived neurotrophic factor and VGF in the hippocampus and prefrontal cortex in mice. We further found that the rapid-acting antidepressant-like effects and the upregulation on brain-derived neurotrophic factor and VGF produced by a low dose of scopolamine (0.025 mg/kg) were completely blocked by verapamil. CONCLUSIONS: These results indicate that L-type voltage-dependent calcium channels are likely involved in the behavioral changes in response to various doses of scopolamine through the regulation of brain-derived neurotrophic factor and VGF levels. Oxford University Press 2017-08-25 /pmc/articles/PMC5793820/ /pubmed/29020410 http://dx.doi.org/10.1093/ijnp/pyx080 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of CINP. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Regular Research Articles Yu, Hanjie Li, Mengmeng Shen, Xinbei Lv, Dan Sun, Xin Wang, Jinting Gu, Xinmei Hu, Jingning Wang, Chuang The Requirement of L-Type Voltage-Dependent Calcium Channel (L-VDCC) in the Rapid-Acting Antidepressant-Like Effects of Scopolamine in Mice |
title | The Requirement of L-Type Voltage-Dependent Calcium Channel (L-VDCC) in the Rapid-Acting Antidepressant-Like Effects of Scopolamine in Mice |
title_full | The Requirement of L-Type Voltage-Dependent Calcium Channel (L-VDCC) in the Rapid-Acting Antidepressant-Like Effects of Scopolamine in Mice |
title_fullStr | The Requirement of L-Type Voltage-Dependent Calcium Channel (L-VDCC) in the Rapid-Acting Antidepressant-Like Effects of Scopolamine in Mice |
title_full_unstemmed | The Requirement of L-Type Voltage-Dependent Calcium Channel (L-VDCC) in the Rapid-Acting Antidepressant-Like Effects of Scopolamine in Mice |
title_short | The Requirement of L-Type Voltage-Dependent Calcium Channel (L-VDCC) in the Rapid-Acting Antidepressant-Like Effects of Scopolamine in Mice |
title_sort | requirement of l-type voltage-dependent calcium channel (l-vdcc) in the rapid-acting antidepressant-like effects of scopolamine in mice |
topic | Regular Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793820/ https://www.ncbi.nlm.nih.gov/pubmed/29020410 http://dx.doi.org/10.1093/ijnp/pyx080 |
work_keys_str_mv | AT yuhanjie therequirementofltypevoltagedependentcalciumchannellvdccintherapidactingantidepressantlikeeffectsofscopolamineinmice AT limengmeng therequirementofltypevoltagedependentcalciumchannellvdccintherapidactingantidepressantlikeeffectsofscopolamineinmice AT shenxinbei therequirementofltypevoltagedependentcalciumchannellvdccintherapidactingantidepressantlikeeffectsofscopolamineinmice AT lvdan therequirementofltypevoltagedependentcalciumchannellvdccintherapidactingantidepressantlikeeffectsofscopolamineinmice AT sunxin therequirementofltypevoltagedependentcalciumchannellvdccintherapidactingantidepressantlikeeffectsofscopolamineinmice AT wangjinting therequirementofltypevoltagedependentcalciumchannellvdccintherapidactingantidepressantlikeeffectsofscopolamineinmice AT guxinmei therequirementofltypevoltagedependentcalciumchannellvdccintherapidactingantidepressantlikeeffectsofscopolamineinmice AT hujingning therequirementofltypevoltagedependentcalciumchannellvdccintherapidactingantidepressantlikeeffectsofscopolamineinmice AT wangchuang therequirementofltypevoltagedependentcalciumchannellvdccintherapidactingantidepressantlikeeffectsofscopolamineinmice AT yuhanjie requirementofltypevoltagedependentcalciumchannellvdccintherapidactingantidepressantlikeeffectsofscopolamineinmice AT limengmeng requirementofltypevoltagedependentcalciumchannellvdccintherapidactingantidepressantlikeeffectsofscopolamineinmice AT shenxinbei requirementofltypevoltagedependentcalciumchannellvdccintherapidactingantidepressantlikeeffectsofscopolamineinmice AT lvdan requirementofltypevoltagedependentcalciumchannellvdccintherapidactingantidepressantlikeeffectsofscopolamineinmice AT sunxin requirementofltypevoltagedependentcalciumchannellvdccintherapidactingantidepressantlikeeffectsofscopolamineinmice AT wangjinting requirementofltypevoltagedependentcalciumchannellvdccintherapidactingantidepressantlikeeffectsofscopolamineinmice AT guxinmei requirementofltypevoltagedependentcalciumchannellvdccintherapidactingantidepressantlikeeffectsofscopolamineinmice AT hujingning requirementofltypevoltagedependentcalciumchannellvdccintherapidactingantidepressantlikeeffectsofscopolamineinmice AT wangchuang requirementofltypevoltagedependentcalciumchannellvdccintherapidactingantidepressantlikeeffectsofscopolamineinmice |