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
Hauptverfasser: Song, Yunjeong, Seo, Sowoon, Lamichhane, Santosh, Seo, Jungwon, Hong, Jin Tae, Cha, Hye Jin, Yun, Jaesuk
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container_title Phytomedicine (Stuttgart)
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creator Song, Yunjeong
Seo, Sowoon
Lamichhane, Santosh
Seo, Jungwon
Hong, Jin Tae
Cha, Hye Jin
Yun, Jaesuk
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]
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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. 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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 ; 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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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