Sauchinone Blocks Ethanol Withdrawal-Induced Anxiety but Spares Locomotor Sensitization: Involvement of Nitric Oxide in the Bed Nucleus of the Stria Terminalis
Both the positive (manifested by locomotor sensitization) and negative (withdrawal symptoms) reinforcing effects of ethanol (EtOH) involve central nitric oxide (NO) signaling. Sauchinone (a bioactive lignan in Saururus chinensis) has been shown to improve methamphetamine-induced behavioral and neuro...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2021-01-01
|
Series: | Evidence-Based Complementary and Alternative Medicine |
Online Access: | http://dx.doi.org/10.1155/2021/6670212 |
id |
doaj-e82aae6ddb124ab6a3c41fc25738b8ea |
---|---|
record_format |
Article |
spelling |
doaj-e82aae6ddb124ab6a3c41fc25738b8ea2021-05-17T00:01:14ZengHindawi LimitedEvidence-Based Complementary and Alternative Medicine1741-42882021-01-01202110.1155/2021/6670212Sauchinone Blocks Ethanol Withdrawal-Induced Anxiety but Spares Locomotor Sensitization: Involvement of Nitric Oxide in the Bed Nucleus of the Stria TerminalisYu Jiao0Sang Chan Kim1Yuhua Wang2Tong Wu3Haifeng Jin4Chul Won Lee5Sook Jahr Park6Bong Hyo Lee7Hee Young Kim8Chae Ha Yang9Zhenglin Zhao10Rongjie Zhao11Department of PsychopharmacologyMedical Research CenterDepartment of PsychopharmacologyDepartment of PsychopharmacologyDepartment of PsychopharmacologyMedical Research CenterMedical Research CenterMedical Research CenterMedical Research CenterMedical Research CenterDepartment of BiochemistryDepartment of PsychopharmacologyBoth the positive (manifested by locomotor sensitization) and negative (withdrawal symptoms) reinforcing effects of ethanol (EtOH) involve central nitric oxide (NO) signaling. Sauchinone (a bioactive lignan in Saururus chinensis) has been shown to improve methamphetamine-induced behavioral and neurochemical changes via the NO signaling pathway. Thus, this study evaluated the effects of sauchinone on locomotor sensitization and anxiety during EtOH withdrawal (EtOHW). Male adult Sprague-Dawley rats were treated with 1.5 g/kg/day of EtOH (20%, vol/vol) via intraperitoneal injection for 28 days, followed by a 3-day withdrawal. During withdrawal, the rats were given intragastric sauchinone (2.5, 7.5, or 25 mg/kg/day) once a day. EtOH locomotor sensitization was determined by challenging EtOHW rats with 0.75 g/kg EtOH, while EtOHW-induced anxiety was assessed using the elevated plus maze (EPM). None of the three doses of sauchinone affected EtOH locomotor sensitization. However, in the EPM, treatment of EtOHW rats with sauchinone at 7.5 or 25 mg/kg/day increased both the number of entries into and the time spent in the open arms. Moreover, the two doses of sauchinone inhibited the oversecretion of plasma corticosterone during EtOHW. In the bed nucleus of the stria terminalis (BNST), EtOHW increased NO production, enhanced gene and protein expression of both inducible nitric oxide synthase (iNOS) and neuronal NOS (nNOS), and also elevated protein levels of corticotropin-releasing factor, which were all inhibited by 25 mg/kg/day sauchinone. In an in vitro experiment, sauchinone (3, 10, and 30 μM) inhibited H2O2-stimulated nNOS protein expression in neuronal PC12 cells. Finally, intra-BNST infusion of sodium nitroprusside, a NO donor, after sauchinone (25 mg/kg/day) administration, abolished its expected anxiolytic effect. Taken together, these results indicate that sauchinone attenuates anxiety-like behavior in rats during EtOHW but spares EtOH locomotor sensitization, and the anxiolytic effect is mediated via the NO signaling pathway in the BNST.http://dx.doi.org/10.1155/2021/6670212 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yu Jiao Sang Chan Kim Yuhua Wang Tong Wu Haifeng Jin Chul Won Lee Sook Jahr Park Bong Hyo Lee Hee Young Kim Chae Ha Yang Zhenglin Zhao Rongjie Zhao |
spellingShingle |
Yu Jiao Sang Chan Kim Yuhua Wang Tong Wu Haifeng Jin Chul Won Lee Sook Jahr Park Bong Hyo Lee Hee Young Kim Chae Ha Yang Zhenglin Zhao Rongjie Zhao Sauchinone Blocks Ethanol Withdrawal-Induced Anxiety but Spares Locomotor Sensitization: Involvement of Nitric Oxide in the Bed Nucleus of the Stria Terminalis Evidence-Based Complementary and Alternative Medicine |
author_facet |
Yu Jiao Sang Chan Kim Yuhua Wang Tong Wu Haifeng Jin Chul Won Lee Sook Jahr Park Bong Hyo Lee Hee Young Kim Chae Ha Yang Zhenglin Zhao Rongjie Zhao |
author_sort |
Yu Jiao |
title |
Sauchinone Blocks Ethanol Withdrawal-Induced Anxiety but Spares Locomotor Sensitization: Involvement of Nitric Oxide in the Bed Nucleus of the Stria Terminalis |
title_short |
Sauchinone Blocks Ethanol Withdrawal-Induced Anxiety but Spares Locomotor Sensitization: Involvement of Nitric Oxide in the Bed Nucleus of the Stria Terminalis |
title_full |
Sauchinone Blocks Ethanol Withdrawal-Induced Anxiety but Spares Locomotor Sensitization: Involvement of Nitric Oxide in the Bed Nucleus of the Stria Terminalis |
title_fullStr |
Sauchinone Blocks Ethanol Withdrawal-Induced Anxiety but Spares Locomotor Sensitization: Involvement of Nitric Oxide in the Bed Nucleus of the Stria Terminalis |
title_full_unstemmed |
Sauchinone Blocks Ethanol Withdrawal-Induced Anxiety but Spares Locomotor Sensitization: Involvement of Nitric Oxide in the Bed Nucleus of the Stria Terminalis |
title_sort |
sauchinone blocks ethanol withdrawal-induced anxiety but spares locomotor sensitization: involvement of nitric oxide in the bed nucleus of the stria terminalis |
publisher |
Hindawi Limited |
series |
Evidence-Based Complementary and Alternative Medicine |
issn |
1741-4288 |
publishDate |
2021-01-01 |
description |
Both the positive (manifested by locomotor sensitization) and negative (withdrawal symptoms) reinforcing effects of ethanol (EtOH) involve central nitric oxide (NO) signaling. Sauchinone (a bioactive lignan in Saururus chinensis) has been shown to improve methamphetamine-induced behavioral and neurochemical changes via the NO signaling pathway. Thus, this study evaluated the effects of sauchinone on locomotor sensitization and anxiety during EtOH withdrawal (EtOHW). Male adult Sprague-Dawley rats were treated with 1.5 g/kg/day of EtOH (20%, vol/vol) via intraperitoneal injection for 28 days, followed by a 3-day withdrawal. During withdrawal, the rats were given intragastric sauchinone (2.5, 7.5, or 25 mg/kg/day) once a day. EtOH locomotor sensitization was determined by challenging EtOHW rats with 0.75 g/kg EtOH, while EtOHW-induced anxiety was assessed using the elevated plus maze (EPM). None of the three doses of sauchinone affected EtOH locomotor sensitization. However, in the EPM, treatment of EtOHW rats with sauchinone at 7.5 or 25 mg/kg/day increased both the number of entries into and the time spent in the open arms. Moreover, the two doses of sauchinone inhibited the oversecretion of plasma corticosterone during EtOHW. In the bed nucleus of the stria terminalis (BNST), EtOHW increased NO production, enhanced gene and protein expression of both inducible nitric oxide synthase (iNOS) and neuronal NOS (nNOS), and also elevated protein levels of corticotropin-releasing factor, which were all inhibited by 25 mg/kg/day sauchinone. In an in vitro experiment, sauchinone (3, 10, and 30 μM) inhibited H2O2-stimulated nNOS protein expression in neuronal PC12 cells. Finally, intra-BNST infusion of sodium nitroprusside, a NO donor, after sauchinone (25 mg/kg/day) administration, abolished its expected anxiolytic effect. Taken together, these results indicate that sauchinone attenuates anxiety-like behavior in rats during EtOHW but spares EtOH locomotor sensitization, and the anxiolytic effect is mediated via the NO signaling pathway in the BNST. |
url |
http://dx.doi.org/10.1155/2021/6670212 |
work_keys_str_mv |
AT yujiao sauchinoneblocksethanolwithdrawalinducedanxietybutspareslocomotorsensitizationinvolvementofnitricoxideinthebednucleusofthestriaterminalis AT sangchankim sauchinoneblocksethanolwithdrawalinducedanxietybutspareslocomotorsensitizationinvolvementofnitricoxideinthebednucleusofthestriaterminalis AT yuhuawang sauchinoneblocksethanolwithdrawalinducedanxietybutspareslocomotorsensitizationinvolvementofnitricoxideinthebednucleusofthestriaterminalis AT tongwu sauchinoneblocksethanolwithdrawalinducedanxietybutspareslocomotorsensitizationinvolvementofnitricoxideinthebednucleusofthestriaterminalis AT haifengjin sauchinoneblocksethanolwithdrawalinducedanxietybutspareslocomotorsensitizationinvolvementofnitricoxideinthebednucleusofthestriaterminalis AT chulwonlee sauchinoneblocksethanolwithdrawalinducedanxietybutspareslocomotorsensitizationinvolvementofnitricoxideinthebednucleusofthestriaterminalis AT sookjahrpark sauchinoneblocksethanolwithdrawalinducedanxietybutspareslocomotorsensitizationinvolvementofnitricoxideinthebednucleusofthestriaterminalis AT bonghyolee sauchinoneblocksethanolwithdrawalinducedanxietybutspareslocomotorsensitizationinvolvementofnitricoxideinthebednucleusofthestriaterminalis AT heeyoungkim sauchinoneblocksethanolwithdrawalinducedanxietybutspareslocomotorsensitizationinvolvementofnitricoxideinthebednucleusofthestriaterminalis AT chaehayang sauchinoneblocksethanolwithdrawalinducedanxietybutspareslocomotorsensitizationinvolvementofnitricoxideinthebednucleusofthestriaterminalis AT zhenglinzhao sauchinoneblocksethanolwithdrawalinducedanxietybutspareslocomotorsensitizationinvolvementofnitricoxideinthebednucleusofthestriaterminalis AT rongjiezhao sauchinoneblocksethanolwithdrawalinducedanxietybutspareslocomotorsensitizationinvolvementofnitricoxideinthebednucleusofthestriaterminalis |
_version_ |
1721438837912109056 |