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1.
D1 dopamine receptor activation required for postsynaptic expression of D2 agonist effects 总被引：15，自引：0，他引：15
J R Walters D A Bergstrom J H Carlson T N Chase A R Braun 《Science (New York, N.Y.)》1987,236(4802):719-722
D1 and D2 dopamine receptors exert synergistic effects on the firing rates of basal ganglia neurons and on the expression of stereotyped behavior in rats. Moreover, the ability of D2 agonists to induce changes in basal ganglia single unit activity and spontaneous motor activity is dependent upon the presence of endogenous dopamine to stimulate D1 receptors; in rats treated with alpha-methyl-rho-tyrosine to reduce endogenous dopamine levels, the neurophysiological and behavioral effects of the D2 agonist quinpirole are significantly attenuated, while the effects of nonselective agonists like apomorphine, which stimulate both D1 and D2 receptors, or combinations of a D2 agonist and a D1 agonist are not attenuated. Thus, the previously held view that D2 receptors alone are responsible for evoking the changes in behavior and basal ganglia output induced by nonselective dopamine agonists and endogenous dopamine is not supported by these results, which indicate that these phenomena require concurrent stimulation of both dopamine receptor subtypes. 相似文献
2.
Rocheville M Lange DC Kumar U Patel SC Patel RC Patel YC 《Science (New York, N.Y.)》2000,288(5463):154-157
Somatostatin and dopamine are two major neurotransmitter systems that share a number of structural and functional characteristics. Somatostatin receptors and dopamine receptors are colocalized in neuronal subgroups, and somatostatin is involved in modulating dopamine-mediated control of motor activity. However, the molecular basis for such interaction between the two systems is unclear. Here, we show that dopamine receptor D2R and somatostatin receptor SSTR5 interact physically through hetero-oligomerization to create a novel receptor with enhanced functional activity. Our results provide evidence that receptors from different G protein (heterotrimeric guanine nucleotide binding protein)-coupled receptor families interact through oligomerization. Such direct intramembrane association defines a new level of molecular crosstalk between related G protein-coupled receptor subfamilies. 相似文献
3.
Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics 总被引：12，自引：0，他引：12
D F Wong H N Wagner L E Tune R F Dannals G D Pearlson J M Links C A Tamminga E P Broussolle H T Ravert A A Wilson J K Toung J Malat J A Williams L A O'Tuama S H Snyder M J Kuhar A Gjedde 《Science (New York, N.Y.)》1986,234(4783):1558-1563
In postmortem studies of patients with schizophrenia, D2 dopamine receptors in the basal ganglia have been observed to be more numerous than in patients with no history of neurological or psychiatric disease. Because most patients with schizophrenia are treated with neuroleptic drugs that block D2 dopamine receptors in the caudate nucleus, it has been suggested that this increase in the number of receptors is a result of adaptation to these drugs rather than a biochemical abnormality intrinsic to schizophrenia. With positron emission tomography (PET), the D2 dopamine receptor density in the caudate nucleus of living human beings was measured in normal volunteers and in two groups of patients with schizophrenia--one group that had never been treated with neuroleptics and another group that had been treated with these drugs. D2 dopamine receptor densities in the caudate nucleus were higher in both groups of patients than in the normal volunteers. Thus, schizophrenia itself is associated with an increase in brain D2 dopamine receptor density. 相似文献
4.
Spontaneous orofacial dyskinesia and dopaminergic function in rats after 6 months of neuroleptic treatment 总被引：3，自引：0，他引：3
A syndrome of spontaneous orofacial dyskinesia was identified in groups of rats treated for 6 months with a wide range of neuroleptic drugs. Phenothiazines, thioxanthenes, and substituted benzamides were particularly likely to induce the syndrome. It was observed in the presence of a functional blockade of dopamine receptors and endured for at least 2.5 months after drug withdrawal. There was no relation between the syndrome and changes in striatal dopamine receptors, as indexed by the binding of tritiated spiperone and tritiated cis(Z)-flupenthixol. The syndrome parallels several of the features of clinical tardive dyskinesia, whose pathophysiology thus may not involve changes in the characteristics of striatal dopamine receptors. 相似文献
5.
The dorsal striatum plays a role in consummatory food reward, and striatal dopamine receptors are reduced in obese individuals, relative to lean individuals, which suggests that the striatum and dopaminergic signaling in the striatum may contribute to the development of obesity. Thus, we tested whether striatal activation in response to food intake is related to current and future increases in body mass and whether these relations are moderated by the presence of the A1 allele of the TaqIA restriction fragment length polymorphism, which is associated with dopamine D2 receptor (DRD2) gene binding in the striatum and compromised striatal dopamine signaling. Cross-sectional and prospective data from two functional magnetic resonance imaging studies support these hypotheses, which implies that individuals may overeat to compensate for a hypofunctioning dorsal striatum, particularly those with genetic polymorphisms thought to attenuate dopamine signaling in this region. 相似文献
6.
Chronic blockade of dopamine D2 receptors, a common mechanism of action for antipsychotic drugs, down-regulates D1 receptors in the prefrontal cortex and, as shown here, produces severe impairments in working memory. These deficits were reversed in monkeys by short-term coadministration of a D1 agonist, ABT 431, and this improvement was sustained for more than a year after cessation of D1 treatment. These findings indicate that pharmacological modulation of the D1 signaling pathway can produce long-lasting changes in functional circuits underlying working memory. Resetting this pathway by brief exposure to the agonist may provide a valuable strategy for therapeutic intervention in schizophrenia and other dopamine dysfunctional states. 相似文献
7.
Kaneko S Hikida T Watanabe D Ichinose H Nagatsu T Kreitman RJ Pastan I Nakanishi S 《Science (New York, N.Y.)》2000,289(5479):633-637
The physiological role of striatal cholinergic interneurons was investigated with immunotoxin-mediated cell targeting (IMCT). Unilateral cholinergic cell ablation caused an acute abnormal turning behavior. These mice showed gradual recovery but displayed abnormal turning by both excess stimulation and inhibition of dopamine actions. In the acute phase, basal ganglia function was shifted to a hyperactive state by stimulation and suppression of striatonigral and striatopallidal neurons, respectively. D1 and D2 dopamine receptors were then down-regulated, relieving dopamine-predominant synaptic perturbation but leaving a defect in controlling dopamine responses. The acetylcholine-dopamine interaction is concertedly and adaptively regulated for basal ganglia synaptic integration. 相似文献
8.
P Seeman C Ulpian C Bergeron P Riederer K Jellinger E Gabriel G P Reynolds W W Tourtellotte 《Science (New York, N.Y.)》1984,225(4663):728-731
The dopamine hypothesis of schizophrenia was examined by measuring the density of dopamine receptors in the postmortem brains of 81 control subjects and 59 schizophrenics from four different countries. The densities of dopamine receptors in the tissues from the schizophrenic patients had a bimodal distribution in the caudate nucleus, putamen, and nucleus accumbens. One mode occurred 25 percent above the control density, and a second mode occurred at a density 2.3 times that of the control density for all three regions. Although almost all the patients had been medicated with neuroleptics, the two modes had the same dissociation constant for the labeled ligand used, suggesting that the neuroleptic doses were similar for the two populations of schizophrenics. The results thus provide direct evidence for two distinct categories of schizophrenia. 相似文献
9.
Imaging dopamine receptors in the human brain by positron tomography 总被引：14，自引：0，他引：14
H N Wagner H D Burns R F Dannals D F Wong B Langstrom T Duelfer J J Frost H T Ravert J M Links S B Rosenbloom S E Lukas A V Kramer M J Kuhar 《Science (New York, N.Y.)》1983,221(4617):1264-1266
Neurotransmitter receptors may be involved in a number of neuropsychiatric disease states. The ligand 3-N-[11C]methylspiperone, which preferentially binds to dopamine receptors in vivo, was used to image the receptors by positron emission tomography scanning in baboons and in humans. This technique holds promise for noninvasive clinical studies of dopamine receptors in humans. 相似文献
10.
Prefrontal neurons engaged by working memory tasks express a sequence of phasic and tonic activations linked to a train of sensory, mnemonic, and response-related events. Here, we report that the dopamine D2 receptor selectively modulates the neural activities associated with memory-guided saccades in oculomotor delayed-response tasks yet has little or no effect on the persistent mnemonic-related activity, which is instead modulated by D1 receptors. This associates the D2 receptor with a specific component of working memory circuitry and fractionates the modulatory effects of D1 and D2 receptors on the neural machinery of a cognitive process. 相似文献
11.
Dopamine activation of an orphan of the steroid receptor superfamily 总被引：26，自引：0，他引：26
12.
A direct role of dopamine in the rat subthalamic nucleus and an adjacent intrapeduncular area 总被引：2，自引：0，他引：2
L L Brown M H Markman L I Wolfson B Dvorkin C Warner R Katzman 《Science (New York, N.Y.)》1979,206(4425):1416-1418
The subthalamic nucleus, a clinically important component of the extrapyramidal motor system, and a lateral area extending into the peduncle contain catecholamine terminals and dopamine receptors coupled to adenylate cyclase. In addition, dopamine agonists administered in vivo enhance glucose utilization in the region. Thus, neuronal function in this region is directly affected by dopamine and dopaminergic drugs. 相似文献
13.
Neuroleptic-induced decrease in plasma homovanillic acid and antipsychotic activity in schizophrenic patients 总被引：3，自引：0，他引：3
D Pickar R Labarca M Linnoila A Roy D Hommer D Everett S M Paul 《Science (New York, N.Y.)》1984,225(4665):954-957
Plasma-free homovanillic acid, a major metabolite of dopamine, was measured in chronically ill schizophrenic patients both before and during treatment with the antipsychotic phenothiazine, fluphenazine. Neuroleptic treatment was associated with a significant time-dependent decrease in plasma homovanillic acid from pretreatment values, which were significantly elevated when compared with those of age- and sex-matched healthy control subjects. Further, both the absolute concentrations as well as the neuroleptic-induced reductions in plasma homovanillic acid determined over 5 weeks of neuroleptic treatment were statistically significantly correlated with ratings of psychosis and improvement in psychosis, respectively. These findings suggest that the delayed effects of neuroleptic agents on presynaptic dopamine activity may more closely parallel their therapeutic actions than do their immediate effects in blocking postsynaptic dopamine receptors and that a decrease in dopamine "turnover" may be responsible for their antipsychotic effects. 相似文献
14.
Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET 总被引：16，自引：0，他引：16
D2 dopamine receptors in the putamen of living human subjects were characterized by using the selective, high-affinity D2 dopamine receptor antagonist carbon-11-labeled raclopride and positron emission tomography. Experiments in four healthy men demonstrated saturability of [11C]raclopride binding to an apparently homogeneous population of sites with Hill coefficients close to unity. In the normal putamen, maximum binding ranged from 12 to 17 picomoles per cubic centimeter and dissociation constants from 3.4 to 4.7 nanomolar. Maximum binding for human putamen at autopsy was 15 picomoles per cubic centimeter. Studies of [11C]raclopride binding indicate that clinically effective doses of chemically distinct neuroleptic drugs result in 85 to 90 percent occupancy of D2 dopamine receptors in the putamen of schizophrenic patients. 相似文献
15.
Lezcano N Mrzljak L Eubanks S Levenson R Goldman-Rakic P Bergson C 《Science (New York, N.Y.)》2000,287(5458):1660-1664
The synergistic response of cells to the stimulation of multiple receptors has been ascribed to receptor cross talk; however, the specific molecules that mediate the resultant signal amplification have not been defined. Here a 24-kilodalton single transmembrane protein, designated calcyon, we functionally characterize that interacts with the D1 dopamine receptor. Calcyon localizes to dendritic spines of D1 receptor-expressing pyramidal cells in prefrontal cortex. These studies delineate a mechanism of Gq- and Gs-coupled heterotrimeric GTP-binding protein-coupled receptor cross talk by which D1 receptors can shift effector coupling to stimulate robust intracellular calcium (Ca2+i) release as a result of interaction with calcyon. The role of calcyon in potentiating Ca2+-dependent signaling should provide insight into the D1 receptor-modulated cognitive functions of prefrontal cortex. 相似文献
16.
目的 评价分析长沙重性精神疾病社区药物治疗的安全性。方法 以社区药物治疗的365例重性精神病患者为对象,对3次锥体外系副反应量表（rating scale for extratyramidal side effects,RSESE）、异常不自主运动量表（abnomal involuntary movement scale,AIMS）、精神性不良反应量表（udvalg for kliniske under-sogelser,UKU）及实验室、心电图检查统计分析以探讨药物治疗安全性。结果 3次RSESE评分值比较无统计学意义;第1、3次AIMS评分值比较有统计学意义（P<0.05）;第1次与第2、3次UKU评分值比较有统计学意义（P<0.05）;第1、3次血常规间、第1次与第2或3次血糖间、第1或2次与第3次血脂间、第1、2次肾功能间比较有统计学意义（P<0.05）;3次肝功能、激素、心电图比较无统计学意义。锥体外系副反应以震颤、肘强直、固定姿态多见;异常不自主运动副反应以上肢面部、唇口周部多见;精神性不良反应以无力、思睡、注意力下降多见。结论 重性精神疾病社区药物治疗不良反应评估稳定,安全性较高,对药物锥体外系副反应及生化、血象、心电图异常情况,须监测、复诊,以减少不良反应的发生。 相似文献
17.
The prefrontal cortex is involved in the cognitive process of working memory. Local injections of SCH23390 and SCH39166, selective antagonists of the D1 dopamine receptor, into the prefrontal cortex of rhesus monkeys induced errors and increased latency in performance on an oculomotor task that required memory-guided saccades. The deficit was dose-dependent and sensitive to the duration of the delay period. These D1 antagonists had no effect on performance in a control task requiring visually guided saccades, indicating that sensory and motor functions were unaltered. Thus, D1 dopamine receptors play a selective role in the mnemonic, predictive functions of the primate prefrontal cortex. 相似文献
18.
Gomberg J Rubinstein JL Peng Z Creager KC Vidale JE Bodin P 《Science (New York, N.Y.)》2008,319(5860):173
We identified seven locations on or near the transform plate boundary in California where nonvolcanic tremor was triggered by the 2002 Denali earthquake. This result implies that the conditions essential for nonvolcanic tremor exist in a range of tectonic environments. Models explaining tremor typically require conditions endemic to subduction zones, that is, high temperatures and fluid pressures, because previously tremor was nearly exclusively documented in subduction zones. The absence of tremor in geothermal areas is inconsistent with such models. Additionally, we found no correlation between creeping or locked faults and tremor, contrary to predictions of frictional models of tremor. 相似文献
19.
At synapses between cortical pyramidal neurons and principal striatal medium spiny neurons (MSNs), postsynaptic D1 and D2 dopamine (DA) receptors are postulated to be necessary for the induction of long-term potentiation and depression, respectively-forms of plasticity thought to underlie associative learning. Because these receptors are restricted to two distinct MSN populations, this postulate demands that synaptic plasticity be unidirectional in each cell type. Using brain slices from DA receptor transgenic mice, we show that this is not the case. Rather, DA plays complementary roles in these two types of MSN to ensure that synaptic plasticity is bidirectional and Hebbian. In models of Parkinson's disease, this system is thrown out of balance, leading to unidirectional changes in plasticity that could underlie network pathology and symptoms. 相似文献
20.
Adenosine 3',5'-monophosphate content in rat caudate nucleus: demonstration of dopaminergic and adrenergic receptors 总被引：6，自引：0，他引：6
Dopamine, apomorphine, isoproterenol, and norepinephrine each increased the concentration of adenosine 3',5'-monophosphate in slice of rat caudate nucleus. The concentrations of dopamine, apomorphine isoproterenol, and norepinephrine causing half-maximal increases were 60, 150, 0.03 and 30 micromoles per liter, respectively. The effect of dopamine was blocked by fluphenazine, a dopamine receptor antagonist, but not by propranolol, a beta-andrenergic receptor antagonist. Conversely, the effect of isoproterenol was blocked by propranolol but not by fluphenazine. The results suggest that in rat caudate nucleus there are two distinct catecholamine receptors capable of causing increased concentrations of adenosine 3',5'-monophosphate, one having the characteristic of dopamine receptor, and the other having the characteristics of beta-adrenergic receptor. 相似文献