• 제목/요약/키워드: Dopamine D2 receptor

검색결과 132건 처리시간 0.03초

월남전 참전 재향군인에서 도파민 D2 수용체 유전자 다형성과 외상후 스트레스 장애 (D2 Dopamine Receptor (DRD2) Gene Polymorphism and Combat-Related Posttraumatic Stress Disorder in Vietnam Veterans)

  • 이수영;정혜경;김태용;최진희;정문용;소형석;신한상;이시은
    • 대한불안의학회지
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    • 제4권2호
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    • pp.142-147
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    • 2008
  • Objective : Evidence from recent studies supports the role of genetic factors in the development of Posttraumatic Stress Disorder (PTSD). The primary aim of this study is to investigate the association between the dopamine D2 receptor (DRD2) TaqI A polymorphism and PTSD. The second aim is to examine the association between the DRD2 TaqI A polymorphism and clinical symptoms in patients with PTSD. Methods : We recruited 189 Vietnam veterans for participation in this study, among whom 99 were PTSD patients and 90 were control subjects. The presence of the DRD2 TaqI A polymorphism was determined by polymerase chain reaction (PCR). Several standardized research scales were used in the clinical assessment of PTSD, including the Combat Exposure Scale (CES), Clinician Administered PTSD Scale (CAPS), Beck Depression Inventory (BDI), and Clinical Global Impression (CGI). Results : There was no significant difference in the distribution of the DRD2 genotype, frequency and prevalence of the A1 allele, or the frequency of heterozygotes between the patients with PTSD and the controls. In the PTSD group, the patients with the A1 allele (A1A1, A1A2) scored higher on the CAPS-total (p=0.044), CAPS-avoidance symptoms (p=0.016) and BDI (p=0.024) than those without the A1 allele (A2A2). Conclusion : We could not find an association between the dopamine D2 receptor (DRD2) TaqI A polymorphism and PTSD. However, the A1 allele of DRD2 seemsto influence avoidance symptoms in patients with PTSD.

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Regulation of c-fos promoter through interaction between dopamine D3 receptor and RGL, ral GDP dissociation stimulator-like

  • Park, Ju-Ran;Kim, So-Young;Kim, Kyeong-Man
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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    • pp.89.2-89.2
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    • 2003
  • Ral GDP dissociation stimulator (Ral GDS) has been found to be an effector protein of Ras, and Ral, a member of small GTP-binding protein (G protein) superfamily, has been suggested to act downstream of Ras. Ral GDP dissociation stimulator-like (RGL) shares 50% amino acid identity with Ral GDP dissociation stimulator, and assumed to possess similar functional role. Using yeast two-hybrid screening, we found that dopamine D3 receptor interacts with RGL. Since RGL is known to regulate the expression of c-fos promoter, effects of D3R on gene expression of c-fos promoter was studied. (omitted)

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Quinpirole Increases Melatonin-Augmented Pentobarbital Sleep via Cortical ERK, p38 MAPK, and PKC in Mice

  • Hong, Sa-Ik;Kwon, Seung-Hwan;Hwang, Ji-Young;Ma, Shi-Xun;Seo, Jee-Yeon;Ko, Yong-Hyun;Kim, Hyoung-Chun;Lee, Seok-Yong;Jang, Choon-Gon
    • Biomolecules & Therapeutics
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    • 제24권2호
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    • pp.115-122
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    • 2016
  • Sleep, which is an essential part of human life, is modulated by neurotransmitter systems, including gamma-aminobutyric acid (GABA) and dopamine signaling. However, the mechanisms that initiate and maintain sleep remain obscure. In this study, we investigated the relationship between melatonin (MT) and dopamine D2-like receptor signaling in pentobarbital-induced sleep and the intracellular mechanisms of sleep maintenance in the cerebral cortex. In mice, pentobarbital-induced sleep was augmented by intraperitoneal administration of 30 mg/kg MT. To investigate the relationship between MT and D2-like receptors, we administered quinpirole, a D2-like receptor agonist, to MT- and pentobarbital-treated mice. Quinpirole (1 mg/kg, i.p.) increased the duration of MT-augmented sleep in mice. In addition, locomotor activity analysis showed that neither MT nor quinpirole produced sedative effects when administered alone. In order to understand the mechanisms underlying quinpirole-augmented sleep, we measured protein levels of mitogen-activated protein kinases (MAPKs) and cortical protein kinases related to MT signaling. Treatment with quinpirole or MT activated extracellular-signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and protein kinase C (PKC) in the cerebral cortex, while protein kinase A (PKA) activation was not altered significantly. Taken together, our results show that quinpirole increases the duration of MT-augmented sleep through ERK1/2, p38 MAPK, and PKC signaling. These findings suggest that modulation of D2-like receptors might enhance the effect of MT on sleep.

신생아 행동 특성과 Dopamine Transporter 유전자 및 Dopamine D2, D3, D4 수용체 유전자의 다형성 (NEONATAL BEHAVIORAL CHARACTERISTICS AND DOPAMINE TRANSPORTER GENE AND DOPAMINE D2, D3, D4 RECEPTOR GENE POLYMORPHISMS)

  • 박영남;김대광;김성욱
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • 제12권2호
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    • pp.179-191
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    • 2001
  • 연구목적:신생아의 행동 특성과 DAT1, DRD2, DRD3 및 DRD4 유전자 다형성 사이에 연관이 있는지 평가하였다. 방 법:2000년 4월 17일부터 2000년 6월 17일까지 출생한 정상 신생아 114명을 대상으로 하였다. 신생아 행동 평가는 Neonatal Behavioral Assessment Scale(NBAS)을 이용하여 생후 약 18시간에 평가하였으며, 출산시 제대혈액을 채취하여 DAT1, DRD2, DRD3 및 DRD4 유전자 다형성을 검사하였다. DAT1, DRD2, DRD3 및 DRD4 유전자의 유전자형에 따라서 집단 사이에 NBAS 7개 항목 점수를 비교하였다. 결 과:DAT1 유전자는 10/10 유전자형 집단과 비교해서 기타 유전자형 집단이 사회성-상호작용, 상태 조직력 및 상태 조절 능력 항목에서 유의하게 점수가 높았다. DRD2 유전자 Ser311/Cys311 유전자형은 Ser/Ser 유전자형 집단과 기타 유전자형 집단 사이에 NBAS 항목 점수에 유의한 차이가 없었다. DRD2 유전자는 TaqI A 및 TaqI B 유전자형에 의한 집단 사이에 NBAS 항목 점수에 유의한 차이가 없었다. DRD3 유전자는 유전자형에 의한 집단 사이에 NBAS 항목 점수에 유의한 차이가 없었다. DRD4 유전자 promoter 유전자형에 의한 집단 사이에 NBAS 항목 점수에 유의한 차이가 없었다. DRD4 유전자 반복배열이 긴 유전자형 집단은 짧은 유전자형 집단보다 습관화 항목 점수가 유의하게 높았다. 결 론:이러한 성적은 DAT1 및 DRD4 유전자 반복배열 다형성이 신생아 행동 특성에 영향을 미치는 유전적 기전일 가능성을 시사한다.

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Antipsychotics for patients with pain

  • Shin, Sang Wook;Lee, Jin Seong;Abdi, Salahadin;Lee, Su Jung;Kim, Kyung Hoon
    • The Korean Journal of Pain
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    • 제32권1호
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    • pp.3-11
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    • 2019
  • Going back to basics prior to mentioning the use of antipsychotics in patients with pain, the International Association for the Study of Pain (IASP) definition of pain can be summarized as an unpleasant experience, composed of sensory experience caused by actual tissue damage and/or emotional experience caused by potential tissue damage. Less used than antidepressants, antipsychotics have also been used for treating this unpleasant experience as adjuvant analgesics without sufficient evidence from research. Because recently developed atypical antipsychotics reduce the adverse reactions of extrapyramidal symptoms, such as acute dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia caused by typical antipsychotics, they are expected to be used more frequently in various painful conditions, while increasing the risk of metabolic syndromes (weight gain, diabetes, and dyslipidemia). Various antipsychotics have different neurotransmitter receptor affinities for dopamine (D), 5-hydroxytryptamine (5-HT), adrenergic (${\alpha}$), histamine (H), and muscarinic (M) receptors. Atypical antipsychotics antagonize transient, weak $D_2$ receptor bindings with strong binding to the $5-HT_{2A}$ receptor, while typical antipsychotics block long-lasting, tight $D_2$ receptor binding. On the contrary, antidepressants in the field of pain management also block the reuptake of similar receptors, mainly on the 5-HT and, next, on the norepinephrine, but rarely on the D receptors. Antipsychotics have been used for treating positive symptoms, such as delusion, hallucination, disorganized thought and behavior, perception disturbance, and inappropriate emotion, rather than the negative, cognitive, and affective symptoms of psychosis. Therefore, an antipsychotic may be prescribed in pain patients with positive symptoms of psychosis during or after controlling all sensory components.

가토 신장기능에 미치는 뇌실내 Domperidone의 영향 (Influence of Intracerebroventricular Domperidone on Rabbit Renal Function)

  • 김영수
    • 대한약리학회지
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    • 제24권1호
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    • pp.135-145
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    • 1988
  • Dopamine(DA)은 뇌실내 투여시에 항이뇨와 함께 Na 배설증가 경향을 보이며, $D_1$, 및 $D_2$ 두 종류의 중추 Dopamine수용체가 신장기능에 서로 상반되는 영향을 미치고 있음이 시사된 바 있다. 본 연구에서는 선택적 $D_2$ 길항제인 Comperidone(DOM)을 이용하여 중추 $D_2$ 수용체의 역할을 구명코자 하였다. DOM은 측뇌실내로 (icv)투여시 항이뇨 및 Na 배설감소를 초래하였으며 신혈류 및 사구체여과율도 감소하였다. 전신혈압은 약간 증가하였다. 정맥내투여시에는 Na 배설에 변동이 없었다. 신경을 제거한 신장에서는 icv DOM에 의한 신혈류역학적 변동은 제거되었으나 Na 배설은 제신경신장측에서도 정상신장측에서와 같이 감소하였다. DA icv의 항이뇨작용은 DOM 전처치에 의하여 영향받지 아니하였다. $D_2$ 수용체 agonist인 Bromocriptine은 뇌실내 투여시 현저한 이뇨 및 Na 이뇨를 나타냈으나 이 작용은 DOM 전처치로 완전히 차단되었다. 또 다른 형의 $D_2-agonist$인 Apomorphine의 icv 투여는 일과성으로 신혈류역학의 증가와 함께 이뇨 및 Na 배설증가를 초래하였으며, DOM 전처치는 신혈류역학변동에 영향을 주지 못하였으나 뇨량 및 Na배설증가는 DOM 전처치에 의하여 현저하게 감약시켰다. 본 연구는 중추 $D_2$ 수용체가 어떤 체액성 natriuretic factor를 퉁하여 신장에 이뇨 및 Na 배설증가작용을 미치고 있음을 시사하였으며, 중추 $D_1$, 수용체는 신경경로를 통하여 항이뇨적 영향을 미치고 중추 $D_2$ 수용체는 Na 배설증가작용을 매개한다는 가설을 뒷받침하는 증거를 제시하였다.

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Influence of Lead on Repetitive Behavior and Dopamine Metabolism in a Mouse Model of Iron Overload

  • Chang, JuOae;Kueon, Chojin;Kim, Jonghan
    • Toxicological Research
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    • 제30권4호
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    • pp.267-276
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    • 2014
  • Exposures to lead (Pb) are associated with neurological problems including psychiatric disorders and impaired learning and memory. Pb can be absorbed by iron transporters, which are up-regulated in hereditary hemochromatosis, an iron overload disorder in which increased iron deposition in various parenchymal organs promote metal-induced oxidative damage. While dysfunction in HFE (High Fe) gene is the major cause of hemochromatosis, the transport and toxicity of Pb in Hfe-related hemochromatosis are largely unknown. To elucidate the relationship between HFE gene dysfunction and Pb absorption, H67D knock-in Hfe-mutant and wild-type mice were given drinking water containing Pb 1.6 mg/ml ad libitum for 6 weeks and examined for behavioral phenotypes using the nestlet-shredding and marble-burying tests. Latency to nestlet-shredding in Pb-treated wild-type mice was prolonged compared with non-exposed wild-types (p < 0.001), whereas Pb exposure did not alter shredding latency in Hfe-mutant mice. In the marble-burying test, Hfe-mutant mice showed an increased number of marbles buried compared with wild-type mice (p = 0.002), indicating more repetitive behavior upon Hfe mutation. Importantly, Pb-exposed wild-type mice buried more marbles than non-exposed wild-types, whereas the number of marbles buried by Hfe-mutant mice did not change whether or not exposed to Pb. These results suggest that Hfe mutation could normalize Pb-induced behavioral alteration. To explore the mechanism of repetitive behavior caused by Pb, western blot analysis was conducted for proteins involved in brain dopamine metabolism. The levels of tyrosine hydroxylase and dopamine transporter increased upon Pb exposure in both genotypes, whereas Hfe-mutant mice displayed down-regulation of the dopamine transporter and dopamine D1 receptor with D2 receptor elevated. Taken together, our data support the idea that both Pb exposure and Hfe mutation increase repetitive behavior in mice and further suggest that these behavioral changes could be associated with altered dopaminergic neurotransmission, providing a therapeutic basis for psychiatric disorders caused by Pb toxicity.

틱장애와 도파민 D2 수용체 유전자와의 연합 연구 (Association Study between Tic Disorder and Dopamine D2 Receptor Gene Polymorphism in Korean Population)

  • 이소영;조인희;김선미;이민수;정한용
    • 생물정신의학
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    • 제13권4호
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    • pp.299-304
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    • 2006
  • Objectives : The purpose of the present study was to investigate whether the TaqI A polymorphism of dopamine receptor D2 gene(DRD2) is associated with Tourette syndrome(TS) and chronic motor tic disorder(CMT) in Korean population. Methods : DRD2 TaqI A RFLP genotyping was carried out with DNA extracted from blood samples of 75 patients with tic disorders(47 with TS and 28 with CMT) and 90 healthy subjects. Genotype and allelic frequencies for the DRD2 gene polymorphisms of the tic disorder group as a whole were compared to those of the control group. Separating the TS group, thereafter, the frequency of genotypes and alleles were compared to those of the controls. Results : The results demonstrated that genotype and allele distributions for the DRD2 gene polymorphism in the tic disorder as a whole, TS, and control groups were not significantly different. Conclusion : No association was found for DRD2 gene, TS and CMT. The data suggest that DRD2 gene may not be a useful marker for the prediction of the susceptibility of tic disorder.

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