共查询到20条相似文献，搜索用时 31 毫秒
1.
Both impulsivity and novelty-seeking have been suggested to be behavioral markers of the propensity to take addictive drugs. However, their relevance for the vulnerability to compulsively seek and take drugs, which is a hallmark feature of addiction, is unknown. We report here that, whereas high reactivity to novelty predicts the propensity to initiate cocaine self-administration, high impulsivity predicts the development of addiction-like behavior in rats, including persistent or compulsive drug-taking in the face of aversive outcomes. This study shows experimental evidence that a shift from impulsivity to compulsivity occurs during the development of addictive behavior, which provides insights into the genesis and neural mechanisms of drug addiction. 相似文献
2.
Lobo MK Covington HE Chaudhury D Friedman AK Sun H Damez-Werno D Dietz DM Zaman S Koo JW Kennedy PJ Mouzon E Mogri M Neve RL Deisseroth K Han MH Nestler EJ 《Science (New York, N.Y.)》2010,330(6002):385-390
The nucleus accumbens is a key mediator of cocaine reward, but the distinct roles of the two subpopulations of nucleus accumbens projection neurons, those expressing dopamine D1 versus D2 receptors, are poorly understood. We show that deletion of TrkB, the brain-derived neurotrophic factor (BDNF) receptor, selectively from D1+ or D2+ neurons oppositely affects cocaine reward. Because loss of TrkB in D2+ neurons increases their neuronal excitability, we next used optogenetic tools to control selectively the firing rate of D1+ and D2+ nucleus accumbens neurons and studied consequent effects on cocaine reward. Activation of D2+ neurons, mimicking the loss of TrkB, suppresses cocaine reward, with opposite effects induced by activation of D1+ neurons. These results provide insight into the molecular control of D1+ and D2+ neuronal activity as well as the circuit-level contribution of these cell types to cocaine reward. 相似文献
3.
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
4.
Bäckman L Nyberg L Soveri A Johansson J Andersson M Dahlin E Neely AS Virta J Laine M Rinne JO 《Science (New York, N.Y.)》2011,333(6043):718
Updating of working memory has been associated with striato-frontal brain regions and phasic dopaminergic neurotransmission. We assessed raclopride binding to striatal dopamine (DA) D2 receptors during a letter-updating task and a control condition before and after 5 weeks of updating training. Results showed that updating affected DA activity before training and that training further increased striatal DA release during updating. These findings highlight the pivotal role of transient neural processes associated with D2 receptor activity in working memory. 相似文献
5.
Cloning and expression of a cocaine-sensitive dopamine transporter complementary DNA 总被引：41，自引：0，他引：41
S Shimada S Kitayama C L Lin A Patel E Nanthakumar P Gregor M Kuhar G Uhl 《Science (New York, N.Y.)》1991,254(5031):576-578
A rat dopamine (DA) transporter complementary DNA has been isolated with combined complementary DNA homology and expression approaches. The DA transporter is a 619-amino acid protein with 12 hydrophobic putative membrane-spanning domains and homology to the norepinephrine and gamma-aminobutyric acid transporters. The expressed complementary DNA confers transport of [3H]DA in Xenopus oocytes and in COS cells. Binding of the cocaine analog [3H]CFT ([3H]2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane) to transfected COS cell membranes yields a pharmacological profile similar to that in striatal membranes. 相似文献
6.
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
7.
试验研究了百草枯引起胎鼠动脉管收缩与肾上腺皮质激素及其受体的关系。结果表明:百草枯对未切除肾上腺的孕鼠胎儿动脉管具有明显的收缩作用,试验组与对照组比较差异显著(P<0.05);百草枯促使未切除肾上腺的孕鼠胎儿血浆中肾上腺皮质激素浓度显著升高,试验组与对照组比较差异显著(P<0.05);妊娠20 d和21 d胎鼠动脉管内皮细胞中存在肾上腺皮质激素受体,这说明百草枯引起胎鼠动脉管收缩与肾上腺皮质激素及其受体有关。 相似文献
8.
Cocaine receptors on dopamine transporters are related to self-administration of cocaine 总被引：77，自引：0，他引：77
Although cocaine binds to several sites in the brain, the biochemical receptor mechanism or mechanisms associated with its dependence producing properties are unknown. It is shown here that the potencies of cocaine-like drugs in self-administration studies correlate with their potencies in inhibiting [3H]mazindol binding to the dopamine transporters in the rat striatum, but not with their potencies in binding to a large number of other presynaptic and postsynaptic binding sites. Thus, the cocaine receptor related to substance abuse is proposed to be the one associated with dopamine uptake inhibition. 相似文献
9.
L-NAME在大鼠失血性低血压期间对多巴胺与去甲肾上腺素升压效应的影响 总被引：1，自引：0，他引：1
目的：观察大鼠失血性低血压期间，一氧化氮（NO）和一氧化氮合酶减少对多巴胺（DA）与去甲肾上腺素（NE）升压效应的影响。方法；戊巴比妥钠麻醉的SD大鼠24只，随机分为DA实验组与对照组各5只，NE实验组与对照组各7只。实验组失血前静脉注射NG－nitro－L－argininemethylester（L－NAME，1mg／kg体重），回输血液后静脉注射L－arginine（L－Arg，100mg／kg体重），对照组不作任何处理。股动脉抽血使平均动脉压（MAP）降至5．0kPa左右，维持120min，于低血压期间，每隔30min，及回输血液后10min，静脉注射L－Arg后10min等时间点，静脉注射DA（20μg／kg体重）或NE（10μg／kg体重）。结果：经L－NAME处理的大鼠，存活时间延长，回输血液后，BP基本恢复至失血前水平，无论在低血压期间或血液回输后，对DA、NE的升压反应均增强，实验组MAP回升值明显高于对照组（P＜0．05），L－Arg可抑制此作用。心率（HR）反应在L－NAME处理鼠与对照鼠之间无差异。结论。在重度失血性低血压期间，L－NAME可以增强血管对DA、NE等缩血管药物的敏感性，在动物的存活和血管张力的调节方面起有益作用。 相似文献
10.
Treatment efforts for cocaine addiction are hampered by high relapse rates. To map brain areas underlying relapse, we used electrical brain stimulation and intracranial injection of pharmacological compounds after extinction of cocaine self-administration behavior in rats. Electrical stimulation of the hippocampus containing glutamatergic fibers, but not the medial forebrain bundle containing dopaminergic fibers, elicited cocaine-seeking behavior dependent on glutamate in the ventral tegmental area. This suggests a role for glutamatergic neurotransmission in relapse to cocaine abuse. The medial forebrain bundle electrodes supported intense electrical self-stimulation. These findings suggest a dissociation of neural systems subserving positive reinforcement (self-stimulation) and incentive motivation (relapse). 相似文献
11.
Dommett E Coizet V Blaha CD Martindale J Lefebvre V Walton N Mayhew JE Overton PG Redgrave P 《Science (New York, N.Y.)》2005,307(5714):1476-1479
Unexpected, biologically salient stimuli elicit a short-latency, phasic response in midbrain dopaminergic (DA) neurons. Although this signal is important for reinforcement learning, the information it conveys to forebrain target structures remains uncertain. One way to decode the phasic DA signal would be to determine the perceptual properties of sensory inputs to DA neurons. After local disinhibition of the superior colliculus in anesthetized rats, DA neurons became visually responsive, whereas disinhibition of the visual cortex was ineffective. As the primary source of visual afferents, the limited processing capacities of the colliculus may constrain the visual information content of phasic DA responses. 相似文献
12.
Witten IB Lin SC Brodsky M Prakash R Diester I Anikeeva P Gradinaru V Ramakrishnan C Deisseroth K 《Science (New York, N.Y.)》2010,330(6011):1677-1681
Cholinergic neurons are widespread, and pharmacological modulation of acetylcholine receptors affects numerous brain processes, but such modulation entails side effects due to limitations in specificity for receptor type and target cell. As a result, causal roles of cholinergic neurons in circuits have been unclear. We integrated optogenetics, freely moving mammalian behavior, in vivo electrophysiology, and slice physiology to probe the cholinergic interneurons of the nucleus accumbens by direct excitation or inhibition. Despite representing less than 1% of local neurons, these cholinergic cells have dominant control roles, exerting powerful modulation of circuit activity. Furthermore, these neurons could be activated by cocaine, and silencing this drug-induced activity during cocaine exposure (despite the fact that the manipulation of the cholinergic interneurons was not aversive by itself) blocked cocaine conditioning in freely moving mammals. 相似文献
13.
Although the voluntary intake of drugs of abuse is a behavior largely preserved throughout phylogeny, it is currently unclear whether pathological drug use ("addiction") can be observed in species other than humans. Here, we report that behaviors that resemble three of the essential diagnostic criteria for addiction appear over time in rats trained to self-administer cocaine. As in humans, this addiction-like behavior is present only in a small proportion of subjects using cocaine and is highly predictive of relapse after withdrawal. These findings provide a new basis for developing a true understanding and treatment of addiction. 相似文献
14.
大豆DNA片段导入玉米自交系提高蛋白质含量的研究 总被引：2，自引：0，他引：2
杜娟 《山西农业大学学报(自然科学版)》2004,24(2):108-111
采用花粉管通道法把大豆DNA片段导入玉米骨干自交系,对诱变玉米籽粒材料进行了籽粒总蛋白含量及醇溶蛋白和谷蛋白含量的测定。结果表明:(1)处理后的38个材料总蛋白含水量都比较高,与各自的对照相比,除1DA2、1DA6上、1DA3、26DB1、26DA4外差异都达显著或极显著水平;(2)醇溶蛋白含量测定中,选了4个处理材料,其中1DA5、26DB4、26DC6含量都比对照高,5DB2含量较对照降低了8 76%;(3)谷蛋白含量测定中,1DA5、26DB4的含量较对照低,5DB2、26DC6的含量比对照高,其中5DB2的增加比例达到23 7%。上述结果初步证明高蛋白特性是可遗传的,这为选育高蛋白玉米新自交系提供了新材料,也为利用外源DNA直接导入技术创造玉米新种质开辟了新途径。 相似文献
15.
Vitamin D deficiency inhibits pancreatic secretion of insulin 总被引：15，自引：0，他引：15
The effects of a vitamin D deficiency on insulin and glucagon release was determined in the isolated perfused rat pancreas by radioimmunoassay of the secreted proteins. During a 30-minute period of perfusion with glucose and arginine, pancreases from vitamin D-deficient rats exhibited a 48 percent reduction in insulin secretion compared to that for pancreases from vitamin D-deficient rats that had been replenished with vitamin D. Vitamin D status had no effect on pancreatic glucagon secretion. This result, along with the previously demonstrated presence in the pancreas of a vitamin D-dependent calcium-binding protein and cytosol receptor for the hormonal form of vitamin D, 1,25-dihydroxyvitamin D3, indicates an important role for vitamin D in the endocrine functioning of the pancreas. 相似文献
16.
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
17.
Compulsive drug use in the face of adverse consequences is a hallmark feature of addiction, yet there is little preclinical evidence demonstrating the actual progression from casual to compulsive drug use. Presentation of an aversive conditioned stimulus suppressed drug seeking in rats with limited cocaine self-administration experience, but no longer did so after an extended cocaine-taking history. In contrast, after equivalent extended sucrose experience, sucrose seeking was still suppressed by an aversive conditioned stimulus. Persistent cocaine seeking in the presence of signals of environmental adversity after a prolonged cocaine-taking history was not due to impaired fear conditioning, nor to an increase in the incentive value of cocaine, and may reflect the establishment of compulsive behavior. 相似文献
18.
目的 研究舒肝解郁胶囊对抑郁模型大鼠脑内5-HT、DA及其代谢产物水平的影响。方法 将28只雄性SD大鼠随机分成正常对照组、模型组、舒肝解郁组、氟西汀组四组;采用慢性轻度不可预见性应激（CUMS）结合孤养方式建立抑郁大鼠模型,舒肝解郁组和氟西汀组大鼠于造模同时分别给予舒肝解郁胶囊和氟西汀干预;用库仑阵列电化学高效液相色谱法分别检测大鼠内侧前额叶皮质（mPFC）及海马CA3区 5-HT、DA及其代谢产物的含量。结果 应激21 d后,模型组与正常对照组比较,大鼠mPFC区5-HT、5－羟吲哚乙酸（5-HIAA）、DA和高香草酸（HVA）的浓度均显著降低,差异有统计学意义（P<0.01）,海马CA3区5-HT、DA和5-HIAA的浓度均显著降低,差异有统计学意义（P<0.05）;与模型组比较,舒肝解郁组和氟西汀组可显著增加大鼠mPFC区5-HT 、DA和HVA浓度,差异有统计学意义（P<0.01或P<0.05）,海马CA3区5-HT、DA和5-HIAA浓度显著升高,差异有统计学意义（P<0.05）。结论 舒肝解郁胶囊能增强抑郁模型大鼠中枢5－HT和 DA神经递质系统的功能,这可能是其抗抑郁作用的神经生化机制之一。 相似文献
19.
Genetic control of susceptibility to experimental allergic encephalomyelitis in rats 总被引：17，自引：0，他引：17
Rats of the inbred strains Lewis and DA are highly susceptible to the induction of experimental allergic encephalomyelitis (EAE) while Brown Norway rats are resistant to this disease. Evidence has been obtained which suggests that a single dominant gene is associated with susceptibility to EAE. The locus controlling EAE susceptibility is closely linked to the Ag-B histocompatibility locus but is not identical to it. 相似文献
20.
Cloning of a serotonin transporter affected by antidepressants 总被引：35，自引：0，他引：35
A complementary DNA clone for a serotonin (5HT) transporter has been isolated from rat basophilic leukemia cells. The complementary DNA sequence predicts a 653-amino acid protein with 12 to 13 putative transmembrane domains. The 5HT transporter has significant homology to the gamma-aminobutyric acid, dopamine, and norepinephrine transporters. Uptake by CV-1 cells expressing the transporter complementary DNA resembles 5HT uptake by platelets and brain synaptosomes; it is sensitive to antidepressants, amphetamine derivatives, and cocaine. 相似文献