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...

Descripción completa

Detalles Bibliográficos
Autores principales: Yu, Hanjie, Li, Mengmeng, Shen, Xinbei, Lv, Dan, Sun, Xin, Wang, Jinting, Gu, Xinmei, Hu, Jingning, Wang, Chuang
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