• 제목/요약/키워드: locomotor

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Evaluation of the Abuse Potential of Novel Amphetamine Derivatives with Modifications on the Amine (NBNA) and Phenyl (EDA, PMEA, 2-APN) Sites

  • Custodio, Raly James Perez;Botanas, Chrislean Jun;Yoon, Seong Shoon;de la Pena, June Bryan;dela Pena, Irene Joy;Kim, Mikyung;Woo, Taeseon;Seo, Joung-Wook;Jang, Choon-Gon;Kwon, Yong Ho;Kim, Nam Yong;Lee, Yong Sup;Kim, Hee Jin;Cheong, Jae Hoon
    • 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.

최근 척수손상 백서에서 인체지방조직유래 중간엽 줄기세포 이식 및 성장호르몬의 투여가 신경회복에 미치는 영향 (The Effect of Human Adipose Tissue Derived Mesenchymal Stem Cells and Growth Hormone on the Recovery of Neurological Deficits due to Experimental Spinal Cord Injury in Rat)

  • 이근철;문인선;허정;권용석;김석권;손희동
    • Archives of Plastic Surgery
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    • 제35권1호
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    • pp.13-19
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    • 2008
  • Purpose: Human adipose tissue-derived mesenchymal stem cells(hATSCs) can be differentiated into multiple mesenchymal lineages, including bone, cartilage, and muscle. And growth hormone play important roles in the normal growth and development of the CNS. In this study, we explored whether the transplanted hATSCs and growth hormones could improve functional recoveries from rats with contusive spinal cord injury. Methods: We divided 30 female rats, which were subjected to a weight driven implant spinal cord injury, into 3 groups with 10 rats each; Group A as a control group, group B with hATSCs transplantation on injured region, and group C with hATSCs transplantation and GH administration for 7 days. Then, we researched their neurologic functional recoveries before and 2, 4, and 8 weeks after transplantation using Basso-Beattie-Bresnahan (BBB) locomotor rating scale. And we checked Y-chromosome positive cells by FISH(Fluorescent in situ hybridization) to identify the survival of transplanted mesenchymal stem cells. Results: After 4 weeks of transplantation, the group B and group C showed significant improvement of neurologic function on BBB locomotor rating scale in comparison with the group A(Group A: $13.1{\pm}0.58$, Group B: $14.6{\pm}0.69$, Group C: $14.9{\pm}0.56$). Moreover, the group C displayed meaningful recovery of neurologic function after 8 weeks in comparison with group B (Group B: $15.7{\pm}0.63$, Group C: $16.5{\pm}1.14$). The group A, the control one, improved for 5 weeks after injury, and had no more recovery. On the other hand, Group B and C showed the improvement of neurologic function continuously for 9 weeks after injury. Conclusion: In this study, we found out that hATSCs transplantation have an effect on neurologic functional recovery of spinal cord injured rat and GH injection seems to bring the synergistic results on this good tendency.

Quercetin의 항불안 효과: GABA 신경계를 중심으로 (Anxiolytic Effects of Quercetin: Involvement of GABAergic System)

  • 정지욱;이승헌
    • 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.

척수손상 흰 쥐의 운동기능 회복에 미치는 손상부위 직접자극을 통한 기능적 자기자극치료 효과 (The Effect of Direct Functional Magnetic Stimulation of the Lesion on Functional Motor Recovery in Spinal Cord Injured Rat)

  • 조윤우;김수정;박해운;서정민;황세진;장성호;이동규;안상호
    • The Journal of Korean Physical Therapy
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    • 제23권1호
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    • pp.53-58
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    • 2011
  • Purpose: The purpose of this study was to determine the effect of direct functional magnetic stimulation (FMS) of affected spinal cord on motor recovery following spinal cord injury in rats. Methods: After a contusion injury at the spinal level T9 using an NYU Impactor, functional magnetic stimulation was delivered by a magnetic stimulator through a round prototype coil (7 cm in diameter). Stimulation parameters were set as follows: repetition rate = 50 Hz (stimulus intensity 100% = 0.18 T), stimulation time = 20 min. Functional magnetic stimulation was administered twice a day, 5 days per week for 8 weeks starting 4 days after spinal cord injury. Functional magnetic stimulationwas delivered directly to the affected spinal cord. Outcomes of locomotor performance were assessed by the Basso Beattie Bresnahan (BBB) locomotor rating scale and by an inclined plane test weekly for 8 weeks. Results: In the BBB test, hindlimb motor function in the Functional magnetic stimulation group improved significantly more compared to the control group at 3, 4, 6, 7, and 8 weeks (p<0.05). In the inclined plane test, the angle of the plane in the functional magnetic stimulation group increased significantly more compared to the control group at 4, 5, 7, and 8 weeks (p<0.05). Conclusion: Our results demonstrate that direct Functional magnetic stimulation of the lesional site may have beneficial effects on motor improvement after spinal cord injury.

Four Novel Synthetic Tryptamine Analogs Induce Head-Twitch Responses and Increase 5-HTR2a in the Prefrontal Cortex in Mice

  • Abiero, Arvie;Ryu, In Soo;Botanas, Chrislean Jun;Custodio, Raly James Perez;Sayson, Leandro Val;Kim, Mikyung;Lee, Hyun Jun;Kim, Hee Jin;Seo, Joung-Wook;Cho, Min Chang;Lee, Kun Won;Yoo, Sung Yeun;Jang, Choon-Gon;Lee, Yong Sup;Cheong, Jae Hoon
    • Biomolecules & Therapeutics
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    • 제28권1호
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    • pp.83-91
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    • 2020
  • Tryptamines are monoamine alkaloids with hallucinogenic properties and are widely abused worldwide. To hasten the regulations of novel substances and predict their abuse potential, we designed and synthesized four novel synthetic tryptamine analogs: Pyrrolidino tryptamine hydrochloride (PYT HCl), Piperidino tryptamine hydrochloride (PIT HCl), N,N-dibutyl tryptamine hydrochloride (DBT HCl), and 2-Methyl tryptamine hydrochloride (2-MT HCl). Then, we evaluated their rewarding and reinforcing effects using the conditioned place preference (CPP) and self-administration (SA) paradigms. We conducted an open field test (OFT) to determine the effects of the novel compounds on locomotor activity. A head-twitch response (HTR) was also performed to characterize their hallucinogenic properties. Lastly, we examined the effects of the compounds on 5-HTR1a and 5-HTR2a in the prefrontal cortex using a quantitative real-time polymerase chain reaction (qRT-PCR) assay. None of the compounds induced CPP in mice or initiated SA in rats. PYT HCl and PIT HCl reduced the locomotor activity and elevated the 5-HTR1a mRNA levels in mice. Acute and repeated treatment with the novel tryptamines elicited HTR in mice. Furthermore, a drug challenge involving a 7-day abstinence from drug use produced higher HTR than acute and repeated treatments. Both the acute treatment and drug challenge increased the 5-HTR2a mRNA levels. Ketanserin blocked the induced HTR. Taken together, the findings suggest that PYT HCl, PIT HCl, DBT HCl, and 2-MT HCl produce hallucinogenic effects via 5-HTR2a stimulation, but may have low abuse potential.

Further Evidence in Support of Psychotropic Action on Red Ginseng

  • Yoshimura, Hiroyuki;Kimura, Naoto
    • 고려인삼학회:학술대회논문집
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    • 고려인삼학회 1990년도 Proceedings of International Symposium on Korean Ginseng, 1990, Seoul, Korea
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    • pp.29-35
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    • 1990
  • Using an ethopharmacological technique, we demonstrated that saponin fraction from red ginseng root possessed a potent psychotropic actions on either intermale or maternal aggression models. A series of experiments clearly indicated that one of psychoactive ingredient is ginsenoside Rbl. Although a drug-induced debilitation of motor performance remains a possible cause of the antiaggressive effect of the drug, ginsenoside Rb 1 did not alter the locomotor activity of the mice during agonistic confrontations. Thus, one can eliminate the possibility that the psychoactive effect of ginsenoside Rbl might be concealed by a drugindulced impairment of motor performance. More recently, we developed a new model for copulatory disorder and introduced into the behavioral analysis of drug action. Male mice which has been housed individually from weaning for 5 weeks failed to manifest copulatory behavior when they encountered with the sexually-receptive females. Daily administration of crude ginseng saponin during isolation housing period prevented the development of copulatory disorder, whereas both ginsenoside Rbl and Rgl were ineffective. A further experiment may be needed to explore active ingredient of ginseng saponins. Keywords Panax ginseng, Korean red ginseng, psychotropic action, saponin, ginsenoside Rb1

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The Effects of KR-10876, a new Quinolone Antimicrobial Agent, on the Central Nervous System

  • Kim, Eun-Joo;Cha, Shin-Woo;Shin, Hwa-Sup;Roh, Jung-Koo;Park, Myoung-Whan;Kim, Wan-Joo
    • Archives of Pharmacal Research
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    • 제16권1호
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    • pp.6-12
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    • 1993
  • To evaluate KR-10876, a new fluoroquinolone antibacterial agent, its effects on the central nervous system(CNS) were investigated in mmice as part of phamacological study, and the results were compared with those for ciprofloxacin and ofloxacin, two prototypes of quinolone antiabctrial agents. All the parameters indicative of CNS function and acute toxicity were measured by close observation of the animals at regular time intervals after oral treatment of test compounds. KR-10876 did not have any effect on the parameters measured at lower does (100, 300 mg/kg, p.o.), it caused ptosis, suppressed spontaneous locomotor activity, hypothemia, and prolonged hexobarbital-induced sleeping time. KR-10876 also had a slight effect on motor coordination only at high dose. Simialr to ciprofloxacin, KR-10876 did not protect mice from pentylenetetrazol-strychnine-, and electroshock-inducedl convulsions at doses tested. These findings demonstrate that KR-10876 affects CNS functions only at high doses. The rank order for effects is ofloxacin$\le$KR-10876>ciprofloxacin.

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Photoreception for Photoperiodism and Circadian Rhythms in the Blow Fly

  • Shiga, Sakiko;Numata, Hideharu
    • Journal of Photoscience
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    • 제9권2호
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    • pp.13-16
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    • 2002
  • A comparison of the functional components underlying photoperiodism and circadian rhythmicity in the same species is an interesting issue in the context of unravelling clock mechanisms. In the present study, covering or surgical removal of the compound eyes was performed to localize photoreceptors for photoperiodism to control reproductive diapause and for entrainment of circadian locomotor rhythms in the blow fly Protophormia terraenovae. Intact flies showed a long-day photoperiodic response. When the compound eyes were covered by silver paint, diapause incidence increased under diapause-averting conditions of a long-day photoperiod and constant light, as if flies were kept under constant darkness. Covering of a medial region of the head capsule or solvent painting of the compound eyes gave no significant effects. When the compound eyes were removed, flies did not distinguish the photoperiod, whereas removal of antennal lobes or ocelli did not affect the photoperiodism. Intact flies showed a freerunning rhythm under constant darkness. The rhythm entrained to light-dark (LD) cycles with light of high and low intensity. When the compound eyes and ocelli were surgically removed, the rhythm entrained to LD cycles with light of high intensity but freeran under LD cycles with light of low intensity. The results suggest the retinal pathways are involved in photoperiodism and that flies use both retinal and extraretinal pathways for rhythm entrainment. Under dim light-LD cycles, the retinal pathways mainly mediate rhythm entrainment. Retinal photoreceptors seem to be used both for photoperiodism and entrainment of the rhythm.

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주자독서환(朱子讀書丸)의 아밀로이드베타로 유발된 생쥐 알츠하이머모델에 대한 효과 (Effects of Jujadokseo-hwan on Mice with Alzheimer's Disease Induced by $Amyloid-{\beta}$)

  • 임강현;고흥;경혁수
    • 대한한방내과학회지
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    • 제27권1호
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    • pp.253-264
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    • 2006
  • Object: This research investigated effects of Jujadokseo-hwan on mice with Alzheimer's Disease induced by $amyloid-{\beta}$. According to Dongyibogam, Jujadokseo-hwan can cure amnesia. Amyloid-B is believed to induce oxidative stress and inflammation in the brain, postulated to play important roles in the pathogenesis of Alzheimer's disease. In this way $Amyloid-{\beta}$ induces Alzheimer's Disease. Methods : In order to make an efficient prescription and cope with dementia, learning and memory functions of mice were tested on passive avoidance test and V-maze task. $NF-{\kappa}B$ were measured from protein derived from the brain. RT-PCR was done for !gene analysis. Primers were protein kinase Band $NGF-{\alpha}$. Results : 1. Jujadokseo-hwan was effective for memory capacity on passive avoidance test. but noneffective for spatial memory capacity and locomotor activity on Y -maze task. 2. The measurement of $NF-{\kappa}B$ showed upward tendancies and the result of RT-PCR showed up-regulation when given Jujadokseo-hwan by mouth. Conclusion: Results suggest that Jujadokseo-hwan is effective on mice with Alzheimer's Disease induced by $amyloid-{\beta}$.

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Effects of Herbal Bath on Functional Recovery and c-Fos Expression in the Ventrolateral Periaqueductal Gray Region of the Brain after Sciatic Crushed-Nerve Injury in Rats

  • Ryu, Moon-Sang;Song, Yun-Kyung;Lim, Hyung-Ho
    • 대한한의학회지
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    • 제27권4호
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    • pp.116-124
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    • 2006
  • Peripheral nerve injuries are a commonly encountered clinical problem and often result in chronic pain and severe functional deficits. At the Dept. of Oriental Rehab. Medicine, we have used for pain control a herbal bath containing the following herbs: Harpagophytum radix, Atractylodes japonica and Corydalis tuber. In the present study, we investigated the effects of this herbal bath on the recovery rate of the locomotor function and the expression of c-Fos in the ventrolateral periaqueductal gray (vIPAG) region of the brain following sciatic crushed nerve injury in rats. In the present study, characteristic gait change with decreasing of the sciatic function index (SFI) was observed and c-Fos expression in the vIPAG was suppressed following sciatic crushed nerve injury in rats. Immersion into herbal bath enhanced SFI value and restored c-Fos expression in the vIPAG to the control value. These results suggest the herbal bath might activate neurons in the vIPAG, and could facilitate functional recovery from peripheral nerve injury.

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