• Title/Summary/Keyword: Dopamine system

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The Pathophysiology of Restless Legs Syndrome/Willis-Ekbom Disease (하지불안증후군/윌리스-엑봄병의 병태생리)

  • Cyn, Jaegong
    • Sleep Medicine and Psychophysiology
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    • v.28 no.2
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    • pp.43-52
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    • 2021
  • Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) is a sleep disorder characterized by sensorimotor symptoms such as unpleasant sensations before sleep, akathisia, and periodic limb movements during sleep. It is also closely related to hyperarousal and is often accompanied by insomnia. Although the mechanism is not clear, the understanding of etiology and pathophysiology has greatly expanded through recent advances in genetic and neurobiological research. The most important pathophysiology of RLS/WED is brain iron deficiency. Such iron deficiency in the brain is caused by complex interactions between several genetic factors and various environmental factors, including comorbidities. Iron deficiency in the brain results in dysfunction of several neurotransmitters. A decrease in adenosine activity appears first, followed by an increase in the activity of glutamate and dopamine. A decrease in adenosine activity and an increase in glutamate activity stimulate the brain arousal system, resulting in hyperarousal. In addition, overproduction of dopamine and glutamate leads to dysfunction of the cortical-striatal-thalamic circuit, resulting in symptoms such as akathisia and periodic limb movements during sleep.

The Role of Spinal Dopaminergic Transmission in the Analgesic Effect of Nefopam on Rat Inflammatory Pain

  • Kim, Do Yun;Chae, Joo Wung;Lim, Chang Hun;Heo, Bong Ha;Park, Keun Suk;Lee, Hyung Gon;Choi, Jeong Il;Yoon, Myung Ha;Kim, Woong Mo
    • The Korean Journal of Pain
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    • v.29 no.3
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    • pp.164-171
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    • 2016
  • Background: Nefopam has been known as an inhibitor of the reuptake of monoamines, and the noradrenergic and/or serotonergic system has been focused on as a mechanism of its analgesic action. Here we investigated the role of the spinal dopaminergic neurotransmission in the antinociceptive effect of nefopam administered intravenously or intrathecally. Methods: The effects of intravenously and intrathecally administered nefopam were examined using the rat formalin test. Then we performed a microdialysis study to confirm the change of extracellular dopamine concentration in the spinal dorsal horn by nefopam. To determine whether the changes of dopamine level are associated with the nefopam analgesia, its mechanism was investigated pharmacologically via pretreatment with sulpiride, a dopaminergic D2 receptor antagonist. Results: When nefopam was administered intravenously the flinching responses in phase I of the formalin test were decreased, but not those in phase II of the formalin test were decreased. Intrathecally injected nefopam reduced the flinching responses in both phases of the formalin test in a dose dependent manner. Microdialysis study revealed a significant increase of the level of dopamine in the spinal cord by intrathecally administered nefopam (about 3.8 fold the baseline value) but not by that administered intravenously. The analgesic effects of intrathecally injected nefopam were not affected by pretreatment with sulpiride, and neither were those of the intravenous nefopam. Conclusions: Both the intravenously and intrathecally administered nefopam effectively relieved inflammatory pain in rats. Nefopam may act as an inhibitor of dopamine reuptake when delivered into the spinal cord. However, the analgesic mechanism of nefopam may not involve the dopaminergic transmission at the spinal level.

Effect of Acupuncture(PC6) on Behavior, Dopamine Release in the Nucleus Accumbens in Rats Sensitized to Morphine (몰핀에 민감화된 흰쥐의 내관부위 자침이 행동과 측핵의 도파민 유리에 미치는 효과)

  • Kim, Sang-Ho;Lyu, Seung-Jun;Kim, Tae-Heon;Kang, Hyung-Won;Lyu, Yeoung-Su
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.4
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    • pp.982-992
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    • 2005
  • Acupuncture as a therapeutic intervention is widely used for the treatment of many functional disorders such as substance abuse and mental dysfunction. Clinical trials are currently underway to determine the effectiveness of acupuncture in the treatment of drug addiction. Yet, there are still many unanswered questions about the basic mechanism of acupuncture. Studies have shown that both the psychomotor stimulant effects and rewarding properties of addictive drugs, including morphine, are sensitized by repeated drug administration and raised the possibility that both of these effects may De linked to the same or closely overlapping the mesolimbic dopamine systems. Neiguan (PC6) point on the pericardium channel which is associated with the brain and its mental function, has been used to treat mental, psychosomatic disorders and gastroenterological disorders. The present study was designed to investigate the effect of acupuncture on repeated morphine-induced changes in extracellular dopamine levels using in vivo microdialysis and to measure the effect of acupuncture on repeated morphine-induced behavioral changes. Male Sprague-Dawley rats were treated twice a day for three days with increasing doses of morphine (10, 20 and 40 mg/kg, s.c.) or with saline. After 15 days of withdrawal, rats were challenged with morphine hydrochloride (5 mg/kg, s.c.). Acupuncture was applied at bilateral Neiguan (PC6) points for 1min after the morphine challenge. Results showed that acupuncture at the specific acupoint PC6, but not at control points (tail and HE8) significantly decreased both dopamine release, behavior induced by a systemic morphine challenge or a single s.c. morphine injection in the morphine-repeated animals. These results suggest that reduction in sensitization may be one mechanism whereby acupuncture alleviates morphine craving in addicts. Moreover, in a more general sense these results suggest that acupuncture can be used as a therapeutic intervention for correcting reversible malfunction of the body by direction of brain pathway and thus acupuncture can contribute to the biochemical balance in the central nervous system by regulating neurotransmitters.

Evaluation of Therapeutic Efficacy using [18F]FP-CIT in 6-OHDA-induced Parkinson's Animal Model

  • Jang Woo Park;Yi Seul Choi;Dong Hyun Kim;Eun Sang Lee;Chan Woo Park;Hye Kyung Chung;Ran Ji Yoo
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.9 no.1
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    • pp.3-8
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    • 2023
  • Parkinson's disease is a neurodegenerative disease caused by damage to brain neurons related to dopamine. Non-clinical animal models mainly used in Parkinson's disease research include drug-induced models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine, and genetically modified transgenic animal models. Parkinson's diagnosis can be made using brain imaging of the substantia nigra-striatal dopamine system and using a radiotracer that specifically binds to the dopamine transporter. In this study, 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane was used to confirm the image evaluation cutoff between normal and parkinson's disease models, and to confirm model persistence over time. In addition, the efficacy of single or combined administration of clinically used therapeutic drugs in parkinson's animal models was evaluated. Image analysis was performed using the PMOD software. Converted to standardized uptake value, and analyzed by standardized uptake value ratio by dividing the average value of left striatum by the average value of right striatum obtained by applying positron emission tomography images to the atlas magnetic resonance template. The image cutoff of the normal and the parkinson's disease model was calculated as SUVR=0.829, and it was confirmed that it was maintained during the test period. In the three-drug combination administration group, the right and left striatum showed a high symmetry of more than 0.942 on average and recovered significantly. Images using 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane are thought to be able to diagnose and evaluate treatment efficacy of non-clinical Parkinson's disease.

An Empirical Analysis of the Active Use Paths induced by YouTube's Personalization Algorithm (유튜브의 개인화 알고리즘이 유도하는 적극이용 경로에 대한 실증분석)

  • Seung-Ju Bae
    • Journal of Korea Society of Industrial Information Systems
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    • v.28 no.2
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    • pp.31-45
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    • 2023
  • This study deals with exploring qualitative steps and paths that appear as YouTube users' usage time increases quantitatively. For the study, I applied theories from psychology and neuroscience, subdivided the interval between the personalization algorithm of the recommendation system, and active use and analyzed the relationship between variables in this process. According to the theory behavioral model theory (FBM), variable reward, and dopamine addiction were applied. Personalization algorithms easy clicks as triggers according to associated content presentation functions in behavioral model theory (FBM). Variable rewards increase motivational effectiveness with unpredictability of the content you search, and dopamine nation is summarized as stimulating the dopaminergic nerve to continuously and actively consume content. This study is expected to make an academic and practical contribution in that it divides the purpose of use of content in the personalization algorithm and active use section into four stages from a psychological perspective: first use, reuse, continuous use, and active use, and analyzes the path.

Korean red ginseng water extract produces antidepressant-like effects through involving monoamines and brain-derived neurotrophic factor in rats

  • Tzu-wen Chou ;Huai-Syuan Huang;Suraphan Panyod ;Yun-Ju Huang ;Lee-Yan Sheen
    • Journal of Ginseng Research
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    • v.47 no.4
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    • pp.552-560
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    • 2023
  • Background: Ginseng Radix (Panax ginseng Meyer, Araliaceae) has been used medicinally to treat the brain and nervous system problems worldwide. Recent studies have revealed physiological effects that could potentially benefit cognitive performance or mood. The present study aimed to investigate the antidepressant effects of Korean red ginseng water extract (KGE) and its active component in an unpredictable chronic mild stress (UCMS)-induced animal model and elucidate the underlying mechanisms. Methods: The antidepressant potential of the UCMS model was evaluated using the sucrose preference test and open field tests. The behavioral findings were further corroborated by the assessment of neurotransmitters and their metabolites from the prefrontal cortex and hippocampus of rats. Three doses of KGE (50, 100, and 200 mg/kg) were orally administered during the experiment. Furthermore, the mechanism underlying the antidepressant-like action of KGE was examined by measuring the levels of brain-derived neurotrophic factor (BDNF)/CREB, nuclear factor erythroid 2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (Keap1) proteins in the prefrontal cortex of UCMS-exposed rats. Results: KGE treatment normalized UCMS-induced depression-related behaviors. Neurotransmitter studies conducted after completing behavioral experiments demonstrated that KGE caused a reduction in the ratio of serotonin and dopamine, indicating a decrease in serotonin and dopamine turnover. Moreover, the expression of BDNF, Nrf2, Keap1 and AKT were markedly increased by KGE in the prefrontal cortex of depressed rats. Conclusion: Our results provide evidence that KGE and its constituents exert antidepressant effects that mediate the dopaminergic and serotonergic systems and expression of BDNF protein in an animal model.

Application of Bioisosterism in Development of Novel Cardiotonics Based on (2'-Aminoethyl)carbostyril and (2'-Aminoethyl)-1-hydroxy-2-pyridone Systems

  • Yoon, Sung-Hwa
    • Journal of Pharmaceutical Investigation
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    • v.22 no.3
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    • pp.49-63
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    • 1992
  • Two different types of chemical manipulations of dobutamine were investigated in order to develop novel, improved cardiotonic drugs. Three new analogues of carbostyril, in which the m-hydroxy group of dobutamine was isosterically modified with an amide type carbostyril system, were synthesized from, ${\rho}-methoxyphenethylamine$ via multi-steps. Two analogues of (2'-aminoethyl)-1-hydroxy-2-pyridone system which has isosteric structural similarity with dopamine without having the COMT vulnerable m-hydroxy group were synthesized via 12 synthetic steps. Their biological stabilities in various media and inotropic activities were evaluated.

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보혈안신탕(補血安神湯), 가미보혈안신탕(加味補血安神湯)의 항(抗) stress효과(效果)에 관(關)한 실험적(實驗的) 연구(硏究)

  • Lee Dong-Jin;Kim Ji-Hyeok;Hwang Ui-Wan
    • Journal of Oriental Neuropsychiatry
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    • v.4 no.1
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    • pp.77-97
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    • 1993
  • Human and animals are living by acclimation to environmental changes like high and cold temperature, nose, confinement, etc. If the above changes reach a defined levels, some physiological abnormal state could appear, which we call them as stress state. Catecholamines are excreted by the sympathetic-adrenomedullary system in free from in urine. Catecholamines are derived from the adrenal medulla and urinary epinephrine can be taken as a rough estemation of the activity of this gland. Many scientist reported the endocrinological change, excretion of catecholamine and its metabolites, stomach ulcer formation, etc. under the condition of the confinement and high temperature. In this study author gave restraint, electric shock and immersion stress to rats by administrating by HPLC and got the following results. 1. In the restriant experiment, epinephrine contents in control rat was 194.7 ng, but in Bohyulanshintang administered rat urine 198.9 ng of epinephrine was found. 2. In the electrical shock experiment, 199.5 ng of epinephrine was found in the control rat urine, but in Bohyulanshintang administered rat urine epinephrine content was 142.4 ng. 3. Dopamine contents in control rat urine the immersion environment was 118.9 ng, but in Bohyulanshintang administered rat urine only 55.2 ng of dopamine was found. 4. Incontrol rat stomach there appeared focal erosion and inflamatory exudate, but in experimental group these symptom were turned to mild condition.

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Phenylethanolamine N-methyltransferase: Regulation of the Enzyme in Adrenal Gland, Brain Stem and Hypothalamus (Phenylethanolamine N-methyltransferase: 부신, 뇌간, 시상하부 효소의 조절)

  • Chun, Yang-Sook;Suh, Yoo-Hun
    • The Korean Journal of Pharmacology
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    • v.32 no.2
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    • pp.159-168
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    • 1996
  • To determine the regulatory mechanism of phenylethanolamine N-methyltransferase (PNMT) in the adrenal gland and in central nervous system, we observed the change of enzyme activity and mRNA level of PNMT in the adrenal gland, the brain stem, and hypothalamus of rats, which were injected with two neuroleptic agents(reserpine and haloperidol ). Reserpine depleting catecholamines in presynaptic vesicle increased PNMT activities in the adrenal gland and the brain stem to 150% of the control in time-dependent manner, but not in the hypothalamus. Haloperidol blocking dopamine receptor decreased PNMT activities in the adrenal gland and the hypothalamus, but not in the brain stem. Thus, the results indicate that catecholamines inhibit synthesis of epinephrine in the brain stem and the adrenal gland, and that dopamine stimulates synthesis of epinephrine in the hypothalamus and the adrenal gland. In addition, since the change of mRNA levels were nearly in accordance with the change of activities, the transcriptional regulation of PNMT is considered the mechanism of the regulation of epinephrine neuron.

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