• Biomolecules & Therapeutics
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• 제23권6호
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• pp.597-603
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• 2015

Synthetic cannabinoids JWH-018 and JWH-250 in 'herbal incense' also called 'spice' were first introduced in many countries. Numerous synthetic cannabinoids with similar chemical structures emerged simultaneously and suddenly. Currently there are not sufficient data on their adverse effects including neurotoxicity. There are only anecdotal reports that suggest their toxicity. In the present study, we evaluated the neurotoxicity of two synthetic cannabinoids (JWH-081 and JWH-210) through observation of various behavioral changes and analysis of histopathological changes using experimental mice with various doses (0.1, 1, 5 mg/kg). In functional observation battery (FOB) test, animals treated with 5 mg/kg of JWH-081 or JWH-210 showed traction and tremor. Their locomotor activities and rotarod retention time were significantly (p<0.05) decreased. However, no significant change was observed in learning or memory function. In histopathological analysis, neural cells of the animals treated with the high dose (5 mg/kg) of JWH-081 or JWH-210 showed distorted nuclei and nucleus membranes in the core shell of nucleus accumbens, suggesting neurotoxicity. Our results suggest that JWH-081 and JWH-210 may be neurotoxic substances through changing neuronal cell damages, especially in the core shell part of nucleus accumbens. To confirm our findings, further studies are needed in the future.

• Environmental Analysis Health and Toxicology
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• 제14권4호
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• pp.217-222
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• 1999

Changes in certain fish behaviors are known to be very sensitive indicators of sublethal exposure to environmental contaminants. Therefore, behavioral toxicity tests, if properly designed, can be very useful to assess the influence of hazardous chemicals on fish. However, quantitative analysis of xenobiotic-mediated changes in locomotor behavior in fishes are rare, due mainly to the methodological difficulties. In general, fish movement has been known to be hypertrophic or hypotrophic according to the chemicals. As a study of fish behavioral toxicities, we qualified the swimming movement of Oryzias latipes using computer-automated video tracking system. Oryzias latipes was exposed to cadmium of 128 mg/L for 1 hour in a limited aquaria, then the total swimming distance, the average swimming velocity, the histogram of turning angles, and the turning frequency were analyzed. Fish treated with cadmium showed decreased swimming activities, decreased velocity, and decreased turning frequency, which means hypotrophic activity. From these results, the computer-automated video tracking system of this study seems to be a good tool for the evaluation of the potential ecotoxicological studies.

• Advances in Traditional Medicine
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• 제9권2호
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• pp.135-141
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• 2009

The purpose of this study was to characterize the putative anxiolytic-like effects of the 70% ethanol extract of Portulaca oleracea (EPO) using an elevated plus maze (EPM) in mice. The EPO was orally administered at 50, 100, 200 or 400 mg/kg to ICR mice, 1 h before the behavioral evaluation in the EPM, respectively. Control mice were treated with an equal volume of 10% tween 80, and positive control mice with diazepam (1 mg/kg). Single treatments of the EPO significantly increased the percentage of time spent and arm entries into the open arms of the EPM versus controls (P < 0.05). Moreover, there were no changes in the locomotor activity and myorelaxant effects in any group compared with the saline controls. In addition, the anxiolytic-like effects of the EPO were blocked by flumazenil (10 mg/kg, i.p), a $GABA_A$ antagonist not by WAY 100635 (0.3 mg/kg, i.p), a 5-$HT_{1A}$ receptor antagonist. These results indicate that P. oleracea is an effective anxiolytic agent, and suggest that the anxiolytic-like effects of P. oleracea is mediated via the GABAergic nervous system.

• Biomolecules & Therapeutics
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• 제25권6호
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• pp.578-585
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• 2017

Recently, there has been a rise in the number of amphetamine derivatives that serve as substitutes for controlled substances (e.g. amphetamine and methamphetamine) on the global illegal drug market. These substances are capable of producing rewarding effects similar to their parent drug. In anticipation of the future rise of new and similar psychoactive substances, we designed and synthesized four novel amphetamine derivatives with N-benzyl, N-benzylamphetamine HCl (NBNA) substituent on the amine region, 1,4-dioxane ring, ethylenedioxy-amphetamine HCl (EDA), methyl, para-methylamphetamine HCl (PMEA), and naphthalene, 2-(aminopropyl) naphthalene HCl (2-APN) substituents on the phenyl site. Then, we evaluated their abuse potential in the conditioned place preference (CPP) test in mice and self-administration (SA) test in rats. We also investigated the psychostimulant properties of the novel drugs using the locomotor sensitization test in mice. Moreover, we performed qRT-PCR analyses to explore the effects of the novel drugs on the expression of D1 and D2 dopamine receptor genes in the striatum. NBNA, but not EDA, PMEA, and 2-APN, induced CPP and SA in rodents. None of the test drugs have produced locomotor sensitization. qRT-PCR analyses demonstrated that NBNA increased the expression of striatal D1 dopamine receptor genes. These data indicate that NBNA yields rewarding effects, suggesting potential for abuse. Continual observation for the rise of related substances is thus strongly encouraged.

• 생명과학회지
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• 제24권3호
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• pp.290-296
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• 2014

이 연구의 목적은 mice를 이용하여 elevated plus-maze (EPM) test와 hole-board test를 통해 quercetin의 잠재적인 항불안 작용을 확인하고자 함이다. Quercetin을 1.25, 2.5, 5나 10 mg/kg의 용량으로 각각 행동시험을 측정하기 1 시간 전에 ICR mice에 경구투여하였다. 대조군은 동일한 양의 10% Tween 80을 투여하였고 양성대조군으로 buspirone 2 mg/kg을 투여하였다. Quercetin을 단회 투여하여 EPM test를 실시한 결과, 5 mg/kg 용량에서 open arm에 머문 시간 및 진입한 횟수의 백분율이 control group과 비교하여 통계적으로 유의성 있게 증가하였다(p<0.05). 또한 quercetin을 투여하여 hole-board test를 실시한 결과, 5 mg/kg 용량에서 구멍에 머리를 넣은 횟수가 control group과 비교하여 통계적으로 유의성 있게 증가하였다(p<0.05). 또한 quercetin와 flumazenil ($GABA_A$ antagonist), WAY-100635 ($GABA_{A-{\rho}}$ antagonist) 또는 trans-4-aminocrotonic acid ($GABA_{A-{\rho}}$ agonist)를 병용투여하여 elevated plus-maze를 실험을 하여 신경계와의 관계를 확인한 결과, trans-4-aminocrotonic acid에서만 quercetin의 항불안 작용이 차단되었음을 확인 할 수 있었다. 결론적으로, 본 연구의 결과에서 quercetin이 elevated plus-maze 및 hole-board test, horizontal wire test, open field test를 통하여 locomotor activity 및 근육이완이나 진정 등의 부작용이 없으면서 우수한 항불안 작용을 가지는 소재라고 생각되며 이러한 작용이 특히 GABA 신경계와 관련이 있음을 시사하고 있다.

• Biomolecules & Therapeutics
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• 제13권2호
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• pp.84-89
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• 2005

The purpose of this study was to characterize the putative anxiolytic-like effects of the aqueous extract of the root of Polygala tenuifolia ( AEPT) using an elevated plus maze (EPM) and hole-board apparatus in mice. The AFPT was orally administered at 50, 100, 200 or 400 mg/kg to ICR mice, 1 h before the behavioral evaluation in the EPM respectively. Control mice were treated with an equal volume of saline, and positive control mice with buspirone (2 mg/kg). Single treatments of the AEPT significantly increased the percentage of time spent and arm entries into the open arms of the EPM vedrsus saline controls (P<0.05). Moreover, there were no changes in the locomotor activity and myorelaxant effects in any group compared with the saline controls. In the hole-board test,single treatments of the AEPT (200 and 400 mg/kg) significantly increased the number of headdips versus saline controls (P<0.05). In addition, the anxiolytic-like effects of the AEPT were blocked by WAY 100635(0.3mg/kg, I.p), a5-$HT_{1A}$ receptor antagonist not by flumazenil, a $GABA_{A}$ antagonist. These results indicate that P. tenuifolia is an effective anxiolytic agent, andsuggest that the anxiolytic-like effects of P. tenuifolia is mediated via the serotonergic nervous system.

• The Journal of Korean Physical Therapy
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• 제24권6호
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• pp.423-427
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• 2012

Purpose: The cerebellum is a region of brain structure that plays an important role in calibrating two different information of neural signal from descending motor commands and from ascending sensory inputs. Damage of the cerebellum shows a variety of classic motor symptoms such as postural and locomotor dysfunctions. Therefore, we tried to investigate motor function and skill in stroke patients with cerebellar lesions in sub-acute stage, and compare with these functions of patients with non-cerebellar lesions. Methods: Total twelve stroke patients with cerebellar lesion and 130 stroke patients with non-cerebellar lesions were retrospectively recruited in this study. For evaluation of motor strength, Motricity index (MI) for upper and lower limbs was tested. For measurement of motor skill function, the modified Brunnstrom classification (MBC), Manual function test (MFT), functional ambulatory category (FAC), and Barthel index were adopted. Results: In comparison of motor strength and motor skill function between two groups, statistical differences between the two groups were significantly observed only in upper MI and FAC. Although no significant differences were found in other variables, stroke patients with cerebellar lesion had higher scores in lower and total MI, MBC, and MFT, whereas they had lower scores in FAC and Barthel index. Conclusion: Our results showed that stroke patients with cerebellar lesion had greater impact on movement functions related to hand motor and walking ability in activities of daily life, compared with patients with non-cerebellar lesion, in spite of similar degree of motor function and skill between the two different lesioned-groups.

• 약학회지
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• 제49권5호
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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.

• International Journal of Contents
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• 제8권1호
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• pp.74-81
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• 2012

The aim is to investigate the analgesic effect of transcranial direct current stimulation(tDCS) on central neuropathic pain(CNP) in spinal cord contusive rat model. Twenty Sprague-Dawley rats($250{\pm}50$ g, male) were used. Thoracic spinal cord(T10) was contused using New York University(NYU) spinal cord impactor. The animals were randomly assigned to two groups; GroupI: Non-treatment after SCI induction(n=10), GroupII: application of tDCS(0.1 mA, 20 min/time, 2 times/day, 5 days/6week) after SCI induction(n=10). Assess the effect of tDCS using the Basso Beattie Bresnahan(BBB) locomotor rating scales, Touch $test^{TM}$ sensory evaluator(TTSE), Plantar test$^{\circledR}$after contusion at the $2^{nd}$, $3^{rd}$, $4^{th}$, $5^{th}$, $6^{th}$ week and the immunohistochemistric response of c-fos in the thalamus, cerebral cortex after contusion at the $3^{rd}$, $6^{th}$ week after SCI. The scores of BBB scales were significantly different from $3^{rd}$week. TTSE were different significantly over time, but there were no differences at each evaluation times on between-measure time effects. Plantar test were different significantly over time and there were difference at the $4^{th}$, $6^{th}$ week after SCI on between-measure time effects. Also, immunohistochemistric response of c-fos was reduced significantly from $3^{rd}$, $6^{th}$ week after SCI in tDCS group compared with control group in thalamus and cortex. These results identified that tDCS of non-invasive therapeutic method may have beneficial analgesic effect on CNP after SCI with behavioral test and immunohistochemical test.

• Journal of Korean Neurosurgical Society
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• 제59권4호
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• pp.334-340
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• 2016

Objective : The aim of our study was to evaluate the neuroprotective functions of the combination therapy using methylprednisolone (MP) and tranilast (TR) after spinal cord injury (SCI) in adult rats. Methods : Spinal cord compression injury model was achieved using Yasargil aneurysm clip. Rats were divided into control group, MP group, TR group, and combination therapy group using TR and MP. Rat models were assessed for locomotor functional recovery using Basso, Beattie, and Bresnahan (BBB) score, spinal cord water content and myeloperoxidase (MPO) activity 24 hours post SCI, haematoxylin and eosin staining and glial fibrillary acid protein (GFAP) staining at 7 and 14 days post SCI. Results : The spinal cord water content and MPO activity in the combination therapy group was significantly lower than the control group and the individual therapy groups p<0.05. The combination therapy group had significantly higher BBB scores than control group and individual therapy groups (p<0.05). At one week after SCI, GFAP expression in the combination group was significantly lower than the control group (p<0.05) but there was no significant difference compared to the individual therapy groups (p>0.05). At 2 weeks after SCI there was a slight decrease in GFAP expression compared to the first week but the difference was not statistically significant (p>0.05), GFAP expression between the groups was not statistically significant p>0.05. Conclusion : Combining MP and TR is therapeutically more effective in improving functional recovery, inhibiting inflammation and glial scar formation after acute SCI.