1.Direct modulation of firing activity by dopamine Dlike receptors in the globus pallidus of both normal and parkinsonian rats.
Yong-Cun ZHU ; Yan XUE ; Hui-Ling DIAO ; Hua CHEN ; Hong-Yun LIU ; Xiao-Hua HAN ; Lei CHEN
Acta Physiologica Sinica 2016;68(5):699-707
The globus pallidus occupies a critical position in the indirect pathway of the basal ganglia circuit, which regulates movement under both normal and pathological conditions. Previous studies have shown that the globus pallidus receives dopaminergic innervation from the axonal collaterals of nigrostriatal fibers. Both dopamine Dand Dlike receptors are expressed in the globus pallidus. The present study was aimed to investigate the direct in vivo electrophysiological effects of dopamine Dlike receptors in the globus pallidus of both normal and parkinsonian rats. Extracellular recordings of multi-barreled microelectrode were used in the present study. In normal rats, micro-pressure ejection of dopamine Dlike receptor agonist quinpirole induced different effects on the firing rate of globus pallidus neurons. In 24 out of the 61 pallidal neurons, quinpirole significantly increased the firing rate by (62.7 ± 11.2)%. In another 16 neurons, quinpirole decreased the spontaneous firing rate by (37.5 ± 2.9)%. Furthermore, co-application of dopamine Dlike receptor antagonist, sulpride, blocked quinpirole-induced modulation of the firing rate of pallidal neurons. On the 6-hydroxydopamine (6-OHDA) lesioned side of parkinsonian rats, quinpirole increased the firing rate in 25 out of the 47 pallidal neurons by (64.2 ± 10.1)%, while decreased the firing rate in 11 neurons by (51.9 ± 6.2)%. Our findings suggest that activation of pallidal dopamine Dlike receptors may bidirectionally modulate the spontaneous firing of globus pallidus neurons in both normal and parkinsonian rats.
Animals
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Disease Models, Animal
;
Dopamine
;
Globus Pallidus
;
metabolism
;
Male
;
Neurons
;
Oxidopamine
;
Parkinsonian Disorders
;
metabolism
;
Rats
;
Receptors, Dopamine D1
;
metabolism
;
Receptors, Dopamine D2
;
metabolism
2.Mechanism of apoptosis-inducing effects of dopamine on K562 leukemia cells.
Lin-Bo YUAN ; Qun HE ; Yi-Min GUO
Journal of Zhejiang University. Medical sciences 2007;36(2):191-195
OBJECTIVETo investigate the mechanism of the apoptosis-inducing effects of dopamine on K562 leukemia cells.
METHODSK562 cells were treated with DP2785, the dopamine receptors were detected with fluorescence spectrophotometer, UV spectrophotometer and fluorescence microscope; the contents of cAMP in K562 cells were measured; and the subtypes of dopamine receptor on K562 cells were analyzed by receptor blocking.
RESULTThe existence of dopamine receptors in K562 cells was demonstrated by fluorescence microscopy, UV spectrophotometer and fluorescence spectrophotometer. Dopamine enhanced the contents of cAMP in K562 cells. Dopamine receptors were blocked by both D1 and D2 antagonists.
CONCLUSIOND1 and D2 dopamine receptors may be involved in dopamine-induced apoptosis of K562 cells, and dopamine can also increase the contents of cAMP in K562 cells.
Apoptosis ; drug effects ; Cyclic AMP ; metabolism ; Dopamine ; pharmacology ; Humans ; K562 Cells ; Microscopy, Fluorescence ; Receptors, Dopamine D1 ; metabolism ; Receptors, Dopamine D2 ; metabolism ; Spectrometry, Fluorescence ; Spectrophotometry, Ultraviolet
3.Parkinson disease drug screening based on the interaction between D(2) dopamine receptor and beta-arrestin 2 detected by capillary zone electrophoresis.
Zheng ZHOU ; Jun-Ming LIAO ; Peng ZHANG ; Jun-Bao FAN ; Jie CHEN ; Yi LIANG
Protein & Cell 2011;2(11):899-905
Parkinson's disease is the second most common neurodegenerative disease in the world. Beta-arrestin-2 has been reported to be an important protein involved in D(2) dopamine receptor desensitization, which is essential to Parkinson's disease. Moreover, the potential value of pharmacological inactivation of G protein-coupled receptor kinase or arrestin in the treatment of patients with Parkinson's disease has recently been shown. We studied the interaction between D(2) dopamine receptor and beta-arrestin-2 and the pharmacological regulation of chemical compounds on such interaction using capillary zone electrophoresis. The results from screening more than 40 compounds revealed three compounds that remarkably inhibit the beta-arrestin-2/D(2) dopamine receptor interaction among them. These compounds are promising therapies for Parkinson's disease, and the method used in this study has great potential for application in large-scale drug screening and evaluation.
Arrestins
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antagonists & inhibitors
;
metabolism
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Dopamine
;
metabolism
;
Dopamine Antagonists
;
therapeutic use
;
Dopamine D2 Receptor Antagonists
;
Drug Evaluation, Preclinical
;
Electrophoresis, Capillary
;
Humans
;
Parkinson Disease
;
drug therapy
;
metabolism
;
pathology
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Receptors, Dopamine D2
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metabolism
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Signal Transduction
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beta-Arrestin 2
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beta-Arrestins
4.The Relationship between the Antipsychotics-Induced Weight Gain and the Dopamine D2, D3, and D4 Receptor Gene Polymorphisms in Korean Schizophrenic Patients.
Hee Cheol KIM ; Sung Won JUNG ; Dae Kwang KIM
Korean Journal of Psychopharmacology 2007;18(5):299-307
OBJECTIVE: Excessive weight gain is often observed during chronic administration of antipsychotic drugs. Several lines of evidences implicate an important role for the dopamine D2 receptor in the regulation of food intake and energy metabolism. Therefore, we investigated the relationship between the antipsychotics-induced weight gain and the polymorphisms in the dopamine D2, D3, and D4 receptor genes (DRD2, DRD33, and DRD4, respectively). METHODS: We conducted a retrospective chart review of 200 consecutively hospitalized patients with the diagnosis of schizophrenia (DSM-IV) treated with various antipsychotics (94% atypical antipsychotics) at Bugok National Hospital, Korea. The patients were divided into two groups, weight gainers (weight gain=5%) and non-gainers (weight gain <5%) by percentile change of body weight at discharge compared to body weight at admission. We investigated the differences of the Ser311Cys polymorphism in the DRD2, the Ser9Gly polymorphism in the DRD3, and the exon III 48 bp repeat polymorphism in the DRD4 between weight gainers and non-gainers. RESULTS: Among the 200 total patients of 200, 73 (36.5%) were categorized as weight gainers. There were no significant differences were observed in the frequencies of DRD2 and DRD4 alleles and genotypes between the weight gainers and non-gainers. However, the weight gainers were associated with carriers of the Gly allele (versus Ser allele) in the Ser9Gly polymorphism of the DRD3 (OR=1.699; 95% CI=1.075~-2.686; p=0.023) and associated with carriers of the Gly/Gly genotype (versus the Ser/Ser genotype) in the Ser9Gly polymorphism of the DRD3 (OR=3.328; 95% CI=1.305~-8.488; p=0.012). CONCLUSION: These results suggest that the Ser9Gly polymorphism of thein DRD3 may have an effect on the mechanism of antipsychotics-induced weight gain in patients with schizophrenia. Further research are needed to replicate these results.
Alleles
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Antipsychotic Agents
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Body Weight
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Diagnosis
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Dopamine*
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Eating
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Energy Metabolism
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Exons
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Genotype
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Humans
;
Korea
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Polymorphism, Genetic
;
Receptors, Dopamine
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Receptors, Dopamine D2
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Retrospective Studies
;
Schizophrenia
;
Weight Gain*
5.Activation of Dopamine D2 Receptors Alleviates Neuronal Hyperexcitability in the Lateral Entorhinal Cortex via Inhibition of HCN Current in a Rat Model of Chronic Inflammatory Pain.
Shi-Hao GAO ; Yong TAO ; Yang ZHU ; Hao HUANG ; Lin-Lin SHEN ; Chang-Yue GAO
Neuroscience Bulletin 2022;38(9):1041-1056
Functional changes in synaptic transmission from the lateral entorhinal cortex to the dentate gyrus (LEC-DG) are considered responsible for the chronification of pain. However, the underlying alterations in fan cells, which are the predominant neurons in the LEC that project to the DG, remain elusive. Here, we investigated possible mechanisms using a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain. We found a substantial increase in hyperpolarization-activated/cyclic nucleotide-gated currents (Ih), which led to the hyperexcitability of LEC fan cells of CFA slices. This phenomenon was attenuated in CFA slices by activating dopamine D2, but not D1, receptors. Chemogenetic activation of the ventral tegmental area -LEC projection had a D2 receptor-dependent analgesic effect. Intra-LEC microinjection of a D2 receptor agonist also suppressed CFA-induced behavioral hypersensitivity, and this effect was attenuated by pre-activation of the Ih. Our findings suggest that down-regulating the excitability of LEC fan cells through activation of the dopamine D2 receptor may be a strategy for treating chronic inflammatory pain.
Animals
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Chronic Pain
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Entorhinal Cortex/metabolism*
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Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
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Neurons/metabolism*
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Rats
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Receptors, Dopamine D1/metabolism*
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Receptors, Dopamine D2
6.The Dynamics of Dopamine D2 Receptor-Expressing Striatal Neurons and the Downstream Circuit Underlying L-Dopa-Induced Dyskinesia in Rats.
Kuncheng LIU ; Miaomiao SONG ; Shasha GAO ; Lu YAO ; Li ZHANG ; Jie FENG ; Ling WANG ; Rui GAO ; Yong WANG
Neuroscience Bulletin 2023;39(9):1411-1425
L-dopa (l-3,4-dihydroxyphenylalanine)-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy for Parkinson's disease. The potential contribution of striatal D2 receptor (D2R)-positive neurons and downstream circuits in the pathophysiology of LID remains unclear. In this study, we investigated the role of striatal D2R+ neurons and downstream globus pallidus externa (GPe) neurons in a rat model of LID. Intrastriatal administration of raclopride, a D2R antagonist, significantly inhibited dyskinetic behavior, while intrastriatal administration of pramipexole, a D2-like receptor agonist, yielded aggravation of dyskinesia in LID rats. Fiber photometry revealed the overinhibition of striatal D2R+ neurons and hyperactivity of downstream GPe neurons during the dyskinetic phase of LID rats. In contrast, the striatal D2R+ neurons showed intermittent synchronized overactivity in the decay phase of dyskinesia. Consistent with the above findings, optogenetic activation of striatal D2R+ neurons or their projections in the GPe was adequate to suppress most of the dyskinetic behaviors of LID rats. Our data demonstrate that the aberrant activity of striatal D2R+ neurons and downstream GPe neurons is a decisive mechanism mediating dyskinetic symptoms in LID rats.
Rats
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Animals
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Levodopa/toxicity*
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Dopamine
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Parkinsonian Disorders/drug therapy*
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Oxidopamine
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Dyskinesia, Drug-Induced
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Corpus Striatum/metabolism*
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Neurons/metabolism*
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Receptors, Dopamine D2/metabolism*
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Antiparkinson Agents/toxicity*
7.mRNA expression of dopamine receptor D2 and dopamine transporter in peripheral blood lymphocytes before and after treatment in children with tic disorder.
Chinese Journal of Contemporary Pediatrics 2016;18(4):297-300
OBJECTIVETo investigate the mRNA expression of dopamine receptor D2 (DRD2) and dopamine transporter (DAT) in peripheral blood lymphocytes before and after treatment in children with tic disorder (TD).
METHODSRT-PCR was used to measure the mRNA expression of DRD2 and DAT in peripheral blood lymphocytes before and after treatment in 60 children with TD. The correlations between mRNA expression of DRD2 and DAT and the severity of TD were analyzed. Sixty healthy children served as the control group.
RESULTSBefore treatment, the children with TD had a significant increase in the mRNA expression of DRD2 and DAT compared with the control group (P<0.05). After 3 months of treatment with oral aripiprazole, the mRNA expression of DRD2 decreased significantly (P<0.05), while that of DAT showed no significant changes in children with TD. In the children with moderate or severe TD, the mRNA expression of DRD2 was positively correlated with Yale Global Tic Severity Scale (YGTSS) score (P<0.05). In the children with moderate TD, the mRNA expression of DAT was positively correlated with YGTSS score (P<0.05).
CONCLUSIONSIn children with TD, the mRNA expression of DRD2 in peripheral blood lymphocytes can be used as one of the indicators for diagnosing TD, assessing the severity of TD, and evaluating clinical outcomes.
Adolescent ; Child ; Child, Preschool ; Dopamine Plasma Membrane Transport Proteins ; genetics ; Female ; Humans ; Lymphocytes ; metabolism ; Male ; RNA, Messenger ; blood ; Receptors, Dopamine D2 ; genetics ; Tic Disorders ; drug therapy ; metabolism ; mortality
8.The protective effect of DR2 activation on hypoxia/reperfusion injury in the neonatal rat cardiomyocytes and related mechanism.
Can WEI ; Jun GAO ; Ai-Dong CHEN ; Shu-Zhi BAI ; Hong-Xia LI ; Lei LIU ; Hong-Jiang SHAO ; Xue PENG ; Mei-Xiu LI ; Chang-Qing XU ; Hong-Zhu LI
Chinese Journal of Applied Physiology 2013;29(4):289-293
OBJECTIVETo observe the effect of dopamine receptor (DR2) activation on hypoxia/reperfusion injury (HRI) in the neonatal rat cardiomyocytes, and to explore its mechanism.
METHODSThe hypoxia/reperfusion (H/R) injury model was established in primarily cultured neonatal rat cardiomyocytes, and randomly assigned: control, H/R, bromocriptine (Bro) and haloperidol (Hal) groups. The cell apoptosis was detected using inverted microscope, transmission electron microscope and flow cytometry (FCM). The lactate dehydrogenase(LDH) and superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in cell medium were analyzed. The expression of mRNA and protein of caspase-3, caspase-8, caspase-9, Fas, Fas-L, Cyt C and Bcl-2 were detected by RT-PCR and Western blot, respectively.
RESULTSCompared with the control group, apoptosis rate, LDH activity, MDA content and the expression of pro-apoptotic factors and anti-apoptotic factors were increased, but SOD activity was decreased in H/R group. Compared with the H/R group, all index above-mentioned were down-regulated or reversed in Bro-group, and had no obvious differences in Hal-group.
CONCLUSIONThe neonatal rat cardiomyocytes injury and apoptosis caused by hypoxia/reperfusion can be inhibited with DR2 activation, which mechanism is related to scavenging oxygen radical.
Animals ; Animals, Newborn ; Apoptosis ; Cell Hypoxia ; Myocardial Reperfusion Injury ; etiology ; metabolism ; Myocytes, Cardiac ; cytology ; metabolism ; Oxidative Stress ; Rats ; Rats, Wistar ; Receptors, Dopamine D2 ; metabolism
9.Effect of Bushen Huoxue Decoction on dopamine D2 receptor in the brain of rats with Parkinson's disease.
Hai-ming WANG ; Ming-hui YANG ; Yong-qi DOU ; Yi LIU ; Shao-dan LI ; Min LI
Journal of Southern Medical University 2011;31(11):1879-1881
OBJECTIVETo explore the mechanism underlying the therapeutic effect of Bushen Huoxue Decoction (BHD), a traditional Chinese medicinal preparation, on dopamine D2 receptor (DRD2) in the brain of rat models of Parkinson's disease (PD).
METHODSA total of 120 SD rats were randomized into normal control group, saline model group and BHD-treated group. In the latter two groups, PD rat models were established by direct injection of 6-OHDA to destruct the substantia nigra compact part (SNC) with corresponding treatments. The behavioral changes of the rats were observed. Radioimmunoassay was employed to determine the changes in the equilibrium dissociation constant (Kd) and maximal binding capacity (B(max)) of DRD2, and immunohistochemistry was used to observe the number of the DRD2-positive cells in the brain of the rats.
RESULTSBHD can markedly improve the behavioral abnormalities of PD model rats. Compared with those in the saline model group, the B(max) of DRD2 in the damaged hemisphere increased while the Kd of BHD decreased significantly after BHD treatment (P<0.01). The number of DRD2-positive cells in BHD-treated group was significantly higher than that in the model group (80.9∓13.59 vs 11.15∓6.78, P<0.01), but showed no significant difference from that in the normal control group (P>0.05).
CONCLUSIONBHD can improve the behavioral abnormalities and increase the cerebral expression and affinity of DRD2 in PD rat models.
Animals ; Brain ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Parkinson Disease ; drug therapy ; metabolism ; Phytotherapy ; Rats ; Receptors, Dopamine D2 ; drug effects ; metabolism
10.Dopamine D2 receptor and transportor corrected in the medial prefrontal contex of morphine-induced conditioned place preference in Sprague-Dawley rats.
Hong-xian CHEN ; Min-jie YE ; Ying WANG ; Rui-ling ZHANG ; Wei HAO ; Chang-qi LI
Journal of Central South University(Medical Sciences) 2008;33(9):784-789
OBJECTIVE:
To investigate the expression of dopamine D2 receptors (D2R) and dopamine transportors (DAT) located in the medial prefrontal contex (mPFC) in high and low conditioned place preference (CPP) rats, and to unveil the possible mechanism leading to different CPP susceptibilities.
METHODS:
One hundred and sixty male Sprague-Dawley rats were randomly assigned into an experiment group (n = 130) and a control group (n = 30). The experiment group was re-classified into 2 groups according to CPP values:high preference group (HP group) and low preference group (LP group). According to the execution time-points after the last administration, the HP and LP group was classified into a 3-hour group (3 h), a 72-hour group (J3d), and a 14-day group (J14d), respectively. At 3 hours, 72 hours, and 14 days after the final injection, rats were killed and cardio-perfused, and the brains were removed and sliced up coronarily. The mRNA levels of D2R and DAT in mPFC were determined with in situ hybridization.
RESULTS:
There were no significant differences of pretest scores staying at the non-preference chamber among the groups(P = 0.470). However, the test scores of the CPP time stayed at pretest natural preference in the HP group were significantly higher than those of the LP group(P = 0.000). In 3h, J3d, and J14d groups,the expressions of D2R mRNA in the HP group (125.43 +/- 2.90 approximately 142.92 +/- 3.32) were lower than those of LP group (122.25 +/- 2.20 approximately 136.67 +/-5.39) (P = 0.000). In 3h and J3d,the expressions of DAT mRNA in the HP group (157.00 +/- 3.55 approximately 145.15 +/- 3.69) were significantly lower than those of the LP group (150.69 +/- 3.12 approximately 138.84 +/- 3.99) (P = 0.000). In J14d, there were no differences among 3 groups in mPFC (P = 0.458).
CONCLUSION
D2R and DAT may be correlated closely and underlie the different susceptibilities to morphine induced CPP.
Animals
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Conditioning, Psychological
;
drug effects
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Disease Susceptibility
;
metabolism
;
Dopamine Plasma Membrane Transport Proteins
;
biosynthesis
;
genetics
;
Male
;
Morphine Dependence
;
metabolism
;
Prefrontal Cortex
;
metabolism
;
RNA, Messenger
;
biosynthesis
;
genetics
;
Random Allocation
;
Rats
;
Rats, Sprague-Dawley
;
Receptors, Dopamine D2
;
biosynthesis
;
genetics