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
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Neurons
;
Oxidopamine
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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.Disulfiram Induced Psychosis.
Satyakam MOHAPATRA ; Nihar Ranjan RATH
Clinical Psychopharmacology and Neuroscience 2017;15(1):68-69
Disulfiram is the commonly prescribed drug for the treatment of alcohol dependence. It's major metabolite (diethyldithiocarbamate) is an inhibitor of dopamine-betahydroxylase, an enzyme that catalyzes the metabolism of dopamine to norepinephrine resulting in psychosis. We recommend that disulfiram should be used at the lowest effective dose, possibly 250 mg daily and caution should be taken while prescribing disulfiram for patients with personal and familial antecedents of psychosis.
Alcoholism
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Disulfiram*
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Dopamine
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Humans
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Metabolism
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Norepinephrine
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Psychotic Disorders*
4.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
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metabolism
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Dopamine
;
metabolism
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Dopamine Antagonists
;
therapeutic use
;
Dopamine D2 Receptor Antagonists
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Drug Evaluation, Preclinical
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Electrophoresis, Capillary
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Humans
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Parkinson Disease
;
drug therapy
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metabolism
;
pathology
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Receptors, Dopamine D2
;
metabolism
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Signal Transduction
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beta-Arrestin 2
;
beta-Arrestins
5.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
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Receptors, Dopamine
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Receptors, Dopamine D2
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Retrospective Studies
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Schizophrenia
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Weight Gain*
6.Blockade of the Dopamine D3 Receptor Attenuates Opioids-Induced Addictive Behaviours Associated with Inhibiting the Mesolimbic Dopamine System.
Rong-Rong HU ; Meng-Die YANG ; Xiao-Yan DING ; Ning WU ; Jin LI ; Rui SONG
Neuroscience Bulletin 2023;39(11):1655-1668
Opioid use disorder (OUD) has become a considerable global public health challenge; however, potential medications for the management of OUD that are effective, safe, and nonaddictive are not available. Accumulating preclinical evidence indicates that antagonists of the dopamine D3 receptor (D3R) have effects on addiction in different animal models. We have previously reported that YQA14, a D3R antagonist, exhibits very high affinity and selectivity for D3Rs over D2Rs, and is able to inhibit cocaine- or methamphetamine-induced reinforcement and reinstatement in self-administration tests. In the present study, our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-administered rats, also attenuated heroin-induced reinstatement of drug-seeking behavior. On the other hand, YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice. Moreover, we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibiting morphine-induced up-regulation of dopaminergic neuron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber photometry recording system. These findings suggest that D3R might play a very important role in opioid addiction, and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors dependent on the dopamine system.
Rats
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Mice
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Animals
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Analgesics, Opioid
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Dopamine
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Heroin/pharmacology*
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Dopamine Antagonists/pharmacology*
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Receptors, Dopamine D3/metabolism*
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Morphine/pharmacology*
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Behavior, Addictive/drug therapy*
;
Self Administration
7.Advance in studies on dopamine system related genetic polymorphisms associated with nicotine dependence.
Chao WANG ; Wei QIAN ; Minming ZHANG
Chinese Journal of Medical Genetics 2014;31(3):334-337
Nicotine is the main component for smoking addiction. It is widely believed that nicotine dependence is heritable. Many studies are committed to study the effects of specific gene polymorphisms connect with nicotine dependence. Release of dopamine has been considered the most important channel for nicotine dependence. This paper provides a review for recent advance in studies on dopamine system related genetic polymorphisms associated with nicotine dependence.
Animals
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Dopamine
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metabolism
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Humans
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Nicotine
;
metabolism
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Polymorphism, Genetic
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Tobacco Use Disorder
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genetics
;
metabolism
8.Differential role of estrogen in dopamine metabolism in the amygdala and striatum of female rats.
Acta Physiologica Sinica 2002;54(2):121-124
To study the effects of estrogen on the contents of dopamine (DA) and its metabolites in the amygdala (Amy) and striatum (Str) of rats, high performance liquid chromatography (HPLC) was used to measure the contents of DA and its metabolites in untreated ovariectomized (OVX) rats and OVX rats treated with estrogen. The contents of DA and its metabolites in Amy but not Str were significantly higher when the OVX rats were treated with a high dose of estradiol benzoate (EB). The turnover rate of DA in Amy of the OVX rats was lower than that of normal and EB-treated OVX rats. The turnover rate of DA in Amy was about twice as high as in the Str, while the content of DA in Amy was only one-sixth of that in the Str. The results obtained imply that serum concentration of estrogen is one of the important factors which affect the DA metabolism and content in the Amy of female rats, while the Str is not influenced by estrogen.
Amygdala
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metabolism
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Animals
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Corpus Striatum
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metabolism
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Dopamine
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metabolism
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Estrogens
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blood
;
physiology
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Female
;
Rats
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Rats, Wistar
9.Dopaminergic Neurons in the Ventral Tegmental-Prelimbic Pathway Promote the Emergence of Rats from Sevoflurane Anesthesia.
Yanping SONG ; Ruitong CHU ; Fuyang CAO ; Yanfeng WANG ; Yanhong LIU ; Jiangbei CAO ; Yongxin GUO ; Weidong MI ; Li TONG
Neuroscience Bulletin 2022;38(4):417-428
Dopaminergic neurons in the ventral tegmental area (VTA) play an important role in cognition, emergence from anesthesia, reward, and aversion, and their projection to the cortex is a crucial part of the "bottom-up" ascending activating system. The prelimbic cortex (PrL) is one of the important projection regions of the VTA. However, the roles of dopaminergic neurons in the VTA and the VTADA-PrL pathway under sevoflurane anesthesia in rats remain unclear. In this study, we found that intraperitoneal injection and local microinjection of a dopamine D1 receptor agonist (Chloro-APB) into the PrL had an emergence-promoting effect on sevoflurane anesthesia in rats, while injection of a dopamine D1 receptor antagonist (SCH23390) deepened anesthesia. The results of chemogenetics combined with microinjection and optogenetics showed that activating the VTADA-PrL pathway prolonged the induction time and shortened the emergence time of anesthesia. These results demonstrate that the dopaminergic system in the VTA has an emergence-promoting effect and that the bottom-up VTADA-PrL pathway facilitates emergence from sevoflurane anesthesia.
Anesthesia
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Animals
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Dopaminergic Neurons/metabolism*
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Rats
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Receptors, Dopamine D1/metabolism*
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Sevoflurane/pharmacology*
;
Ventral Tegmental Area/metabolism*
10.Effect of bushen huoxue granule on dopamine neurotransmitter and dopamine transporter in the brain of patients with Parkinson's disease.
Shao-dan LI ; Ming-hui YANG ; Yi LIU
Chinese Journal of Integrated Traditional and Western Medicine 2011;31(5):622-625
OBJECTIVETo observe the effect of Bushen Huoxue Granule (BHG) on dopamine (DA) neurotransmitter and dopamine transporter (DAT) in the brain of patients with Parkinson's disease (PD) as an adjunctive therapy.
METHODSNinety-four PD patients were randomly assigned to two groups, 47 in each group. Madopar was given to all as the basic treatment group. The placebo was given to those in the control group while BHG was given to those in the treatment. The therapeutic course for all was three months. Before and after treatment DA levels in the brain of patients were detected by encephalofluctuograph (EFG) technique. Changes of DAT in the striatum of patients in the treatment group were detected by positron emission tomography (PET) and region of interest (ROI) analysis.
RESULTS(1) Before treatment the DA level was lower in the two groups than the normal value, showing significant difference (P < 0.01), but with no significant difference between the two groups (P > 0.05). After treatment the DA level obviously increased in the two groups, showing significant difference from that before treatment (P < 0.01). No significant difference existed in the DA level in the two groups when compared with the normal value (P > 0.05), but with significant difference between the two groups (P < 0.05). Better results were obtained in the treatment group than in the control group. (2) The DAT radioactive accumulation inside the striatum increased obviously in the treatment group after treatment. ROI analysis showed the total ratio of striatum/cerebellum before and after treatment was 1.86 +/- 0.32 and 2.61 +/- 0.53 respectively, showing statistical difference (P < 0.05).
CONCLUSIONBHG could improve the DA level of PD patients, and increasing DAT contents in the striatum, thus playing a role in effectively treating PD.
Aged ; Brain ; metabolism ; Dopamine ; metabolism ; Dopamine Plasma Membrane Transport Proteins ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease ; drug therapy ; metabolism ; Phytotherapy