Background: 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.
Hypothesis/purpose: 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.
Study design: 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.
Results: 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.
Conclusion: Our results suggest that limonene inhibits anxiety-related behavior through A2A receptor-mediated regulation of DAergic and GABAergic neuronal activity.
Keywords: Adenosine A2A receptor; Anxiety; Dopamine; GAD-67; Limonene; Tyrosine hydroxylase.
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