• Food Science and Preservation
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• v.19 no.5
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• pp.767-773
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• 2012

The purpose of this study was to investigate the anxiolytic-like effect of the methanol extract of Sophorae fructus (MESF) using elevated plus-maze (EPM), open field test, and horizontal wire test in mice. MESF was orally administered at doses of 50, 100, 200, or 400 mg/kg to ICR mice 1 h before behavioral evaluation. The control group was given an equal volume of 10% Tween 80, and the positive control group was given diazepam (1 mg/kg, i.p.). The administration of MESF significantly increased the percentage of time spent in open arms and the entries into the open arms of the EPM compared with the 10% Tween 80-treated control group (p < 0.05). In addition, the anxiolytic-like activities of MESF were antagonized by flumazenil (a GABAA antagonist, 10 mg/kg) but not by WAY-100635 (a 5-HT1A antagonist, 0.3 mg/kg). Futhermore, there were no changes in the locomotor activity and myorelaxant effects of the experimental group, as opposed to the 10% Tween 80-treated control group. Therefore, these findings suggest that MESF promotes the anxiolytic-like activity mediated by the GABAergic nervous system in mice.

• Journal of Life Science
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• v.24 no.3
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• pp.290-296
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• 2014

The present experiment investigated putative anxiolytic-like effects of quercetin using an elevated plus-maze (EPM) and hole-board apparatus test in mice. Quercetin is a flavonoid widely distributed in nature. Quercetin (1.25, 2.5, 5, or 10 mg/kg) was orally administered to ICR mice 1 h before a behavioral evaluation in the EPM. Control mice were treated with an equal volume of vehicle, and positive control mice were treated with buspirone (2 mg/kg, i.p.). The mice administered quercetin (5 mg/kg) spent a significantly longer percentage of time in the open arms of the EPM and their percentage of entries into the open arms was significantly increased compared to the vehicle-treated controls (p<0.05). The anxiolytic-like activities of quercetin were antagonized by trans-4-aminocrotonic acid (a $GABA_{A-{\rho}}$ agonist, 20 mg/kg) but not by flumazenil (a $GABA_A$ antagonist, 10 mg/kg) or WAY-100635 (a $5-HT_{1A}$ antagonist, 0.3 mg/kg). Moreover, there were no changes in the locomotor activity or myorelaxant effects in any group compared with the vehicle-treated controls. In the hole-board apparatus test, the number of head-dips increased significantly in the single treatment with quercetin (5 mg/kg) group compared to the vehicle-treated controls (p<0.05). These findings suggest that quercetin can promote anxiolytic-like activity, mediated by the GABAergic nervous system, in mice.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.212.1-212.1
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• 2003

The purpose of the this study was to characterize the putative anxiolytic-like effects of the aqueous extract of Albizzia julibrissin stem bark using the elevated plus maze (EPM) in rats. The water extract of Albizzia julibrissin was orally administered at 10, 50, 100 or 200 mg/kg to adult male SD rats, 1 h before behavioral evaluation in an EPM, respectively. Control rats were treated with an equal volume of saline, and positive control rats buspirone (1 mg/kg). Single or repeated treatment (for 7 days) of the water extract of Albizzia julibrissin (at 100 or 200 mg/kg) significantly increased time-spent and arm entries into the open arms of the EPM, and decreased time-spent and arm entries in the closed arms of the EPM versus saline controls (P ＜ 0.05). (omitted)

• YAKHAK HOEJI
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• v.49 no.5
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• pp.437-442
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• 2005

The purpose of this study was to characterize the putative anxiolytic-like effects of phenylpropanoids using the elevated plus maze (EPM) test in mice. Cinnamic acid, p-coumaric acid, caffeic acid and ferulic acid were orally administered to male ICR mice, 1 h before behavioral evaluation in an EPM, respectively. Control mice were treated with an equal volume of vehicle, and positive control mice diazepam (1 mg/kg). A single treatment with phenylpropanoids (at 8 mg/kg) significantly increased time-spent and arm entries into the open arms of the EPM, and decreased time-spent and arm entries into the closed arms of the EPM versus control (P<0.05). However, no changes in the locomotor activity and myorelaxant effect were seen in any group versus the saline control. These results suggest that phenylpropanoids may be an effective anx-iolytic agent.

• Advances in Traditional Medicine
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• v.7 no.1
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• pp.41-45
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• 2007

The roots of the plant Korean ginseng have been extensively used in the traditional Chinese herbal medicine. The effects of chronic administration of Korean ginseng extract (KGE) were investigated on two different anxiety models: the elevated T-maze (for inhibitory avoidance and escape measurements) and the open field test (OFT). Diazepam (1 mg/kg), KGE (10, 30 and 100 mg/kg) were administered orally for 15 days. On the 14th day, mice were previously exposed for 30 min to one of the open arms of the T-maze, 24 h before the test. On 15th day, mice had two exposures to the enclosed and open arm of the elevated T-maze followed by exposure to the open field apparatus. The number of line crossings in the apparatus was used to assess locomotor changes. Cumulative Concentration Response Curve of 5-HT was plotted using rat fundus which were pre-treated in a similar way. Treatment with Diazepam (1 mg/kg) and KGE (10, 30 and 100 mg/kg) significantly (P < 0.05) impaired inhibitory avoidance performance but did not impair escape latency. In OFT, diazepam facilitated locomotion as compared to vehicle and other treatment groups. KGE at any of the selected doses did not impair locomotion. Concentration response curve of 5-HT was shifted towards the right with suppression of maxima in rats treated with KGE. The results suggest that KGE exerts anxiolytic like behaviour in a specific subset of defensive behaviour, particularly those related to generalized anxiety disorder.

• Advances in Traditional Medicine
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• v.6 no.3
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• pp.179-185
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• 2006

We investigated the effects of chronic administration of different extracts of ginger rhizome [pet ether extract (PE); toluene fraction (TF) of pet ether extract] on anxiety models: the elevated T-maze (ETM) (for inhibitory avoidance and escape measurements) and the open field test. Ondansetron (1 mg/kg), FE (10, 30 &100 mg/kg) and TF (10 & 30 mg/kg) were administered orally for 15 days. On the $14^{th}$ day mice were previously exposed for 30 min to one of the open arms of the T-maze, 24 h before the test. On $15^{th}$ day mice had two exposures to the enclosed and open arm of the ETM followed by exposure to the open field apparatus. The number of line crossings in the apparatus was used to assess locomotor changes. Cumulative Concentration Response Curve of 5-HT was plotted using rat fundus which were pretreated in a similar way. Treatment with Ondansetron (1 mg/kg), PE (100 mg/kg), TF (10 mg/kg) and TF (30 mg/kg) significantly (P<0.05) impaired inhibitory avoidance performance but did not impair escape latency. Concentration response curve of 5-HT was shifted towards the right with suppression of maxima in rats treated with PE and TF. The results suggest that PE and TF of Ginger rhizome exerts anxiolytic like behaviour in a specific subset of defensive behaviour, particularly those related to generalized anxiety disorder.

• The Korean Journal of Pain
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• v.28 no.1
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• pp.4-10
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• 2015

Etifoxine (etafenoxine, $Stresam^{(R)}$) is a non-benzodiazepine anxiolytic with an anticonvulsant effect. It was developed in the 1960s for anxiety disorders and is currently being studied for its ability to promote peripheral nerve healing and to treat chemotherapy-induced pain. In addition to being mediated by $GABA_A{\alpha}2$ receptors like benzodiazepines, etifoxine appears to produce anxiolytic effects directly by binding to ${\beta}2$ or ${\beta}3$ subunits of the $GABA_A$ receptor complex. It also modulates $GABA_A$ receptors indirectly via stimulation of neurosteroid production after etifoxine binds to the 18 kDa translocator protein (TSPO) of the outer mitochondrial membrane in the central and peripheral nervous systems, previously known as the peripheral benzodiazepine receptor (PBR). Therefore, the effects of etifoxine are not completely reversed by the benzodiazepine antagonist flumazenil. Etifoxine is used for various emotional and bodily reactions followed by anxiety. It is contraindicated in situations such as shock, severely impaired liver or kidney function, and severe respiratory failure. The average dosage is 150 mg per day for no more than 12 weeks. The most common adverse effect is drowsiness at the initial stage. It does not usually cause any withdrawal syndromes. In conclusion, etifoxine shows less adverse effects of anterograde amnesia, sedation, impaired psychomotor performance, and withdrawal syndromes than those of benzodiazepines. It potentiates $GABA_A$ receptor-function by a direct allosteric effect and by an indirect mechanism involving the activation of TSPO. It seems promising that non-benzodiazepine anxiolytics including etifoxine will replenish shortcomings of benzodiazepines and selective serotonin reuptake inhibitors according to animated studies related to TSPO.

• Biomolecules & Therapeutics
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• v.22 no.3
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• pp.213-222
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• 2014

Abnormal adaptation of the stress-response system following traumatic stress can lead to alterations in the hypothalamic-pituitaryadrenal (HPA) axis that may contribute to the development of post-traumatic stress disorder (PTSD). The present study used several behavioral tests to investigate the anxiolytic-like and antidepressant activity of L-tetrahydropalmatine (L-THP) in an experimental rat model of anxiety and depression induced by single prolonged stress (SPS), an animal model of PTSD. Male rats were treated intraperitoneally (i.p.) with vehicle or varied doses of THP 30 min prior to SPS for 8 consecutive days. Daily THP (50 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index, increased the risk assessment, and increased the number of head dips over the borders of the open arms after SPS. THP was also associated with increased time spent at the center of the open field, reduced grooming behaviors in the EPM test, and reduced time spent immobile in the forced swimming test (FST). It also blocked the decrease in neuropeptide Y (NPY) and the increase in corticotrophin-releasing factor (CRF) expression in the hypothalamus. This is the first study to determine that THP exerts pronounced anxiolytic-like and antidepressant effects on the development of the behavioral and biochemical symptoms associated with PTSD, indicating its prophylactic potential. Thus, THP reversed several behavioral impairments triggered by the traumatic stress of SPS and is a potential non-invasive therapeutic intervention for PTSD.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.1
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• pp.81-87
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• 2019

Ketamine has long been used as an anesthetic agent. However, ketamine use is associated with numerous side effects, including flashbacks, amnesia, delirium, and aggressive or violent behavior. Ketamine has also been abused as a cocktail with ecstasy, cocaine, and methamphetamine. Several studies have investigated therapeutic applications of ketamine, demonstrating its antidepressant and anxiolytic effects in both humans and rodents. We recently reported that neonatal maternal separation causes enhanced anxiety- and aggressive-like behaviors in adolescent. In the present study, we evaluated how acute and chronic ketamine administration affected the behavioral consequences of neonatal maternal separation in adolescent mice. Litters were separated from dams for 4 hours per day for 19 days beginning after weaning. Upon reaching adolescence (post-natal day 35-49), mice were acutely (single injection) or chronically (7 daily injections) treated with a sub-anesthetic dose (15 mg/kg) of ketamine. At least 1 h after administration of ketamine, mice were subjected to open-field, elevated-plus maze, and resident-intruder tests. We found that acute ketamine treatment reduced locomotor activity. In contrast, chronic ketamine treatment decreased anxiety, as evidenced by increased time spent on open arms in the elevated-plus maze, and remarkably reduced the number and duration of attacks. In conclusion, the present study suggests that ketamine has potential for the treatment of anxiety and aggressive or violent behaviors.

• Journal of Ginseng Research
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• v.38 no.4
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• pp.256-263
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• 2014

Background: Korean Red Ginseng (KRG) is known to have antianxiety properties. This study was conducted to investigate the anxiolytic effects of KRG extract (KRGE) during ethanol withdrawal (EW) and the involvement of the mesoamygdaloid dopamine (DA) system in it. Methods: Rats were treated with 3 g/kg/d of ethanol for 28 d, and subjected to 3 d of withdrawal. During EW, KRGE (20 mg/kg/d or 60 mg/kg/d, p.o.) was given to rats once/d for 3 d. Thirty min after the final dose of KRGE, anxiety-like behavior was evaluated in an elevated plus maze (EPM), and plasma corticosterone (CORT) levels were determined by a radioimmunoassay (RIA). In addition, concentrations of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) in the central nucleus of the amygdala (CeA) were also measured by high performance liquid chromatography (HPLC). Results: The EPM test and RIA revealed KRGE inhibited anxiety-like behavior and the over secretion of plasma CORT during EW. Furthermore, the behavioral effect was blocked by a selective DA D2 receptor (D2R) antagonist (eticlopride) but not by a selective DA D1 receptor (D1R) antagonist (SCH23390). HPLC analyses showed KRGE reversed EW-induced decreases of DA and DOPAC in a dose-dependent way. Additionally, Western blotting and real-time polymerase chain reaction (PCR) assays showed that KRGE prevented the EW-induced reductions in tyrosine hydroxylase (TH) protein expression in the CeA and TH mRNA expression in the ventral tegmental area (VTA). Conclusion: These results suggest that KRGE has anxiolytic effects during EW by improving the mesoamygdaloid DA system.