Limonene has anti-anxiety activity via adenosine A2A receptor-mediated regulation of dopaminergic and GABAergic neuronal function in the striatum
Limonene, a common terpene found in citrus fruits, is assumed to reduce stress and mood disorders. Dopamine and γ-aminobutyric acid (GABA) have been reported to play an important role in modulating anxiety in different parts of the brain. Herein, we report the anxiolytic activity of limonene. In add...
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Veröffentlicht in: | Phytomedicine (Stuttgart) 2021-03, Vol.83, p.153474-153474, Article 153474 |
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description | Limonene, a common terpene found in citrus fruits, is assumed to reduce stress and mood disorders. Dopamine and γ-aminobutyric acid (GABA) have been reported to play an important role in modulating anxiety in different parts of the brain.
Herein, we report the anxiolytic activity of limonene. In addition, we identified a possible mechanism underlying the effect of limonene on DAergic and GABAergic neurotransmission.
In this study, mice were injected with saline in the control group and limonene in the test group before behavioral analysis. We performed immunoblotting and high-performance liquid chromatography (HPLC) analysis after the behavioral study.
The limonene treated group showed increased locomotor activity and open-arm preference in the elevated plus maze experiment. Limonene treatment increased the expression of both tyrosine hydroxylase and GAD-67 proteins and significantly upregulated dopamine levels in the striatum. Furthermore, tissue dopamine levels were increased in the striatum of mice following limonene treatment, and depolarization-induced GABA release was enhanced by limonene pre-treatment in PC-12 cells. Interestingly, limonene-induced anxiolytic activity and GABA release augmentation were blocked by an adenosine A2A receptor (A2AR) antagonist.
Our results suggest that limonene inhibits anxiety-related behavior through A2A receptor-mediated regulation of DAergic and GABAergic neuronal activity.
[Display omitted] |
doi_str_mv | 10.1016/j.phymed.2021.153474 |
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Herein, we report the anxiolytic activity of limonene. In addition, we identified a possible mechanism underlying the effect of limonene on DAergic and GABAergic neurotransmission.
In this study, mice were injected with saline in the control group and limonene in the test group before behavioral analysis. We performed immunoblotting and high-performance liquid chromatography (HPLC) analysis after the behavioral study.
The limonene treated group showed increased locomotor activity and open-arm preference in the elevated plus maze experiment. Limonene treatment increased the expression of both tyrosine hydroxylase and GAD-67 proteins and significantly upregulated dopamine levels in the striatum. Furthermore, tissue dopamine levels were increased in the striatum of mice following limonene treatment, and depolarization-induced GABA release was enhanced by limonene pre-treatment in PC-12 cells. Interestingly, limonene-induced anxiolytic activity and GABA release augmentation were blocked by an adenosine A2A receptor (A2AR) antagonist.
Our results suggest that limonene inhibits anxiety-related behavior through A2A receptor-mediated regulation of DAergic and GABAergic neuronal activity.
[Display omitted]</description><identifier>ISSN: 0944-7113</identifier><identifier>EISSN: 1618-095X</identifier><identifier>DOI: 10.1016/j.phymed.2021.153474</identifier><identifier>PMID: 33548867</identifier><language>eng</language><publisher>Germany: Elsevier GmbH</publisher><subject>Adenosine A2A receptor ; Animals ; Anti-Anxiety Agents - pharmacology ; Anxiety ; Anxiety - drug therapy ; Anxiety - metabolism ; Behavior, Animal - drug effects ; Corpus Striatum - drug effects ; Corpus Striatum - metabolism ; Dopamine ; Dopamine - metabolism ; Dopaminergic Neurons - drug effects ; Dopaminergic Neurons - metabolism ; GABAergic Neurons - drug effects ; GABAergic Neurons - metabolism ; GAD-67 ; gamma-Aminobutyric Acid - metabolism ; Limonene ; Limonene - pharmacology ; Locomotion - drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Rats ; Receptor, Adenosine A2A - metabolism ; Synaptic Transmission - drug effects ; Tyrosine 3-Monooxygenase - metabolism ; Tyrosine hydroxylase</subject><ispartof>Phytomedicine (Stuttgart), 2021-03, Vol.83, p.153474-153474, Article 153474</ispartof><rights>2021 Elsevier GmbH</rights><rights>Copyright © 2021 Elsevier GmbH. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-18f6e395e0e9e9df0ac4caefd4348222813abaf0f556db5a47c65a30bf81c0283</citedby><cites>FETCH-LOGICAL-c362t-18f6e395e0e9e9df0ac4caefd4348222813abaf0f556db5a47c65a30bf81c0283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0944711321000167$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33548867$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Song, Yunjeong</creatorcontrib><creatorcontrib>Seo, Sowoon</creatorcontrib><creatorcontrib>Lamichhane, Santosh</creatorcontrib><creatorcontrib>Seo, Jungwon</creatorcontrib><creatorcontrib>Hong, Jin Tae</creatorcontrib><creatorcontrib>Cha, Hye Jin</creatorcontrib><creatorcontrib>Yun, Jaesuk</creatorcontrib><title>Limonene has anti-anxiety activity via adenosine A2A receptor-mediated regulation of dopaminergic and GABAergic neuronal function in the striatum</title><title>Phytomedicine (Stuttgart)</title><addtitle>Phytomedicine</addtitle><description>Limonene, a common terpene found in citrus fruits, is assumed to reduce stress and mood disorders. Dopamine and γ-aminobutyric acid (GABA) have been reported to play an important role in modulating anxiety in different parts of the brain.
Herein, we report the anxiolytic activity of limonene. In addition, we identified a possible mechanism underlying the effect of limonene on DAergic and GABAergic neurotransmission.
In this study, mice were injected with saline in the control group and limonene in the test group before behavioral analysis. We performed immunoblotting and high-performance liquid chromatography (HPLC) analysis after the behavioral study.
The limonene treated group showed increased locomotor activity and open-arm preference in the elevated plus maze experiment. Limonene treatment increased the expression of both tyrosine hydroxylase and GAD-67 proteins and significantly upregulated dopamine levels in the striatum. Furthermore, tissue dopamine levels were increased in the striatum of mice following limonene treatment, and depolarization-induced GABA release was enhanced by limonene pre-treatment in PC-12 cells. Interestingly, limonene-induced anxiolytic activity and GABA release augmentation were blocked by an adenosine A2A receptor (A2AR) antagonist.
Our results suggest that limonene inhibits anxiety-related behavior through A2A receptor-mediated regulation of DAergic and GABAergic neuronal activity.
[Display omitted]</description><subject>Adenosine A2A receptor</subject><subject>Animals</subject><subject>Anti-Anxiety Agents - pharmacology</subject><subject>Anxiety</subject><subject>Anxiety - drug therapy</subject><subject>Anxiety - metabolism</subject><subject>Behavior, Animal - drug effects</subject><subject>Corpus Striatum - drug effects</subject><subject>Corpus Striatum - metabolism</subject><subject>Dopamine</subject><subject>Dopamine - metabolism</subject><subject>Dopaminergic Neurons - drug effects</subject><subject>Dopaminergic Neurons - metabolism</subject><subject>GABAergic Neurons - drug effects</subject><subject>GABAergic Neurons - metabolism</subject><subject>GAD-67</subject><subject>gamma-Aminobutyric Acid - metabolism</subject><subject>Limonene</subject><subject>Limonene - pharmacology</subject><subject>Locomotion - drug effects</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Rats</subject><subject>Receptor, Adenosine A2A - metabolism</subject><subject>Synaptic Transmission - drug effects</subject><subject>Tyrosine 3-Monooxygenase - metabolism</subject><subject>Tyrosine hydroxylase</subject><issn>0944-7113</issn><issn>1618-095X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhS0EotPCGyDkJZsM_kvibJBCBS3SSGxAYmd5nOuOR4kdbGfUeQzeGA9pt6z8991z5HMQekfJlhLafDxu58N5gmHLCKNbWnPRihdoQxsqK9LVv16iDemEqFpK-RW6TulICBVdS16jK85rIWXTbtCfnZuCBw_4oBPWPrtK-0cH-Yy1ye7kyubkNNYD-JBc4XrW4wgG5hxiVfydzjCUm4dl1NkFj4PFQ5j1VOD44EwRHfBd_7lfTx6WGLwesV28-cc7j_MBcMqxSC3TG_TK6jHB26f1Bv38-uXH7X21-3737bbfVYY3LFdU2gZ4VwOBDrrBEm2E0WAHwYVkjEnK9V5bYuu6Gfa1Fq1pas3J3kpqCJP8Bn1YdecYfi-QsppcMjCO2kNYkmJCtkWrkU1BxYqaGFKKYNUc3aTjWVGiLmWoo1rLUJcy1FpGGXv_5LDsL2_PQ8_pF-DTCkD558lBVMk48KaEWhLOagju_w5_AVusoBQ</recordid><startdate>202103</startdate><enddate>202103</enddate><creator>Song, Yunjeong</creator><creator>Seo, Sowoon</creator><creator>Lamichhane, Santosh</creator><creator>Seo, Jungwon</creator><creator>Hong, Jin Tae</creator><creator>Cha, Hye Jin</creator><creator>Yun, Jaesuk</creator><general>Elsevier GmbH</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202103</creationdate><title>Limonene has anti-anxiety activity via adenosine A2A receptor-mediated regulation of dopaminergic and GABAergic neuronal function in the striatum</title><author>Song, Yunjeong ; Seo, Sowoon ; Lamichhane, Santosh ; Seo, Jungwon ; Hong, Jin Tae ; Cha, Hye Jin ; Yun, Jaesuk</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-18f6e395e0e9e9df0ac4caefd4348222813abaf0f556db5a47c65a30bf81c0283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adenosine A2A receptor</topic><topic>Animals</topic><topic>Anti-Anxiety Agents - pharmacology</topic><topic>Anxiety</topic><topic>Anxiety - drug therapy</topic><topic>Anxiety - metabolism</topic><topic>Behavior, Animal - drug effects</topic><topic>Corpus Striatum - drug effects</topic><topic>Corpus Striatum - metabolism</topic><topic>Dopamine</topic><topic>Dopamine - metabolism</topic><topic>Dopaminergic Neurons - drug effects</topic><topic>Dopaminergic Neurons - metabolism</topic><topic>GABAergic Neurons - drug effects</topic><topic>GABAergic Neurons - metabolism</topic><topic>GAD-67</topic><topic>gamma-Aminobutyric Acid - metabolism</topic><topic>Limonene</topic><topic>Limonene - pharmacology</topic><topic>Locomotion - drug effects</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Rats</topic><topic>Receptor, Adenosine A2A - metabolism</topic><topic>Synaptic Transmission - drug effects</topic><topic>Tyrosine 3-Monooxygenase - metabolism</topic><topic>Tyrosine hydroxylase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Song, Yunjeong</creatorcontrib><creatorcontrib>Seo, Sowoon</creatorcontrib><creatorcontrib>Lamichhane, Santosh</creatorcontrib><creatorcontrib>Seo, Jungwon</creatorcontrib><creatorcontrib>Hong, Jin Tae</creatorcontrib><creatorcontrib>Cha, Hye Jin</creatorcontrib><creatorcontrib>Yun, Jaesuk</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Phytomedicine (Stuttgart)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Song, Yunjeong</au><au>Seo, Sowoon</au><au>Lamichhane, Santosh</au><au>Seo, Jungwon</au><au>Hong, Jin Tae</au><au>Cha, Hye Jin</au><au>Yun, Jaesuk</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Limonene has anti-anxiety activity via adenosine A2A receptor-mediated regulation of dopaminergic and GABAergic neuronal function in the striatum</atitle><jtitle>Phytomedicine (Stuttgart)</jtitle><addtitle>Phytomedicine</addtitle><date>2021-03</date><risdate>2021</risdate><volume>83</volume><spage>153474</spage><epage>153474</epage><pages>153474-153474</pages><artnum>153474</artnum><issn>0944-7113</issn><eissn>1618-095X</eissn><abstract>Limonene, a common terpene found in citrus fruits, is assumed to reduce stress and mood disorders. Dopamine and γ-aminobutyric acid (GABA) have been reported to play an important role in modulating anxiety in different parts of the brain.
Herein, we report the anxiolytic activity of limonene. In addition, we identified a possible mechanism underlying the effect of limonene on DAergic and GABAergic neurotransmission.
In this study, mice were injected with saline in the control group and limonene in the test group before behavioral analysis. We performed immunoblotting and high-performance liquid chromatography (HPLC) analysis after the behavioral study.
The limonene treated group showed increased locomotor activity and open-arm preference in the elevated plus maze experiment. Limonene treatment increased the expression of both tyrosine hydroxylase and GAD-67 proteins and significantly upregulated dopamine levels in the striatum. Furthermore, tissue dopamine levels were increased in the striatum of mice following limonene treatment, and depolarization-induced GABA release was enhanced by limonene pre-treatment in PC-12 cells. Interestingly, limonene-induced anxiolytic activity and GABA release augmentation were blocked by an adenosine A2A receptor (A2AR) antagonist.
Our results suggest that limonene inhibits anxiety-related behavior through A2A receptor-mediated regulation of DAergic and GABAergic neuronal activity.
[Display omitted]</abstract><cop>Germany</cop><pub>Elsevier GmbH</pub><pmid>33548867</pmid><doi>10.1016/j.phymed.2021.153474</doi><tpages>1</tpages></addata></record> |
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subjects | Adenosine A2A receptor Animals Anti-Anxiety Agents - pharmacology Anxiety Anxiety - drug therapy Anxiety - metabolism Behavior, Animal - drug effects Corpus Striatum - drug effects Corpus Striatum - metabolism Dopamine Dopamine - metabolism Dopaminergic Neurons - drug effects Dopaminergic Neurons - metabolism GABAergic Neurons - drug effects GABAergic Neurons - metabolism GAD-67 gamma-Aminobutyric Acid - metabolism Limonene Limonene - pharmacology Locomotion - drug effects Male Mice Mice, Inbred C57BL Rats Receptor, Adenosine A2A - metabolism Synaptic Transmission - drug effects Tyrosine 3-Monooxygenase - metabolism Tyrosine hydroxylase |
title | Limonene has anti-anxiety activity via adenosine A2A receptor-mediated regulation of dopaminergic and GABAergic neuronal function in the striatum |
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