多巴胺对正常和吗啡成瘾大鼠疼痛相关电活动的不同作用

目的研究多巴胺对正常大鼠和吗啡成瘾大鼠中枢的伤害性刺激的传递的影响。方法在给予坐骨神经伤害性刺激后,记录中枢痛兴奋神经元的电活动,观察多巴胺对正常大鼠和吗啡成瘾大鼠中枢痛兴奋神经元电活动的影响。结果正常大鼠中,多巴胺使尾核痛兴奋神经元的痛诱发放电潜伏期缩短,说明多巴胺可使正常大鼠尾核痛兴奋神经元的活动增强,多巴胺受体拮抗剂氟哌利多可以阻断这种作用。吗啡大鼠中,多巴胺使尾核痛兴奋神经元的痛诱发放电潜伏期延长,说明多巴胺可使吗啡大鼠尾核痛兴奋神经元的活动减弱。结论脑室注射多巴胺后,正常大鼠和吗啡成瘾大鼠的尾核对痛刺激的反应存在着差异。     

L-365,260对吗啡成瘾大鼠尾核中痛兴奋神经元电活动的影响

目的观察八肽胆囊收缩素(CCK-8)B受体拮抗剂L-365,260对正常及吗啡成瘾大鼠尾核(Cd)中痛兴奋神经元(PEN)电活动的影响,从而进一步探讨中枢CCK-8和尾核在吗啡成瘾大鼠痛觉调制中的作用。方法以电脉冲刺激大鼠坐骨神经作为伤害性痛刺激,用玻璃微电极记录尾核中PEN的放电,观察Cd内注入L-365,260对PEN电活动的影响。结果 L-365,260可降低吗啡成瘾与正常大鼠尾核中PEN的兴奋性,使PEN痛诱发放电频率减少,潜伏期延长。结论 L-365,260对吗啡成瘾及正常大鼠尾核中PEN均呈抑制作用。L-365,260是通过作用于尾核内CCK-B受体增强吗啡镇痛作用。间接证明CCK-8确实参与了大鼠中枢痛觉的调制,CCK-8主要通过激活大鼠尾核中CCK-B受体来下调吗啡镇痛作用的。     

吗啡成瘾大鼠伏核电刺激前后多巴胺含量的变化

目的观察吗啡成瘾大鼠在伏核电刺激前后伏核多巴胺（DA）含量的变化。方法40只实验大鼠随机分为假刺激组（ShS组）、刺激组（DBS组）、吗啡成瘾组（MA组）和生理盐水对照组（NS组）。MA组、ShS组和DBS组大鼠通过腹腔注射盐酸吗啡建立吗啡成瘾大鼠动物模型,NS组大鼠相同方法注射同体积生理盐水。随后ShS组和DBS组大鼠进行双侧伏核电极植入,建立吗啡成瘾大鼠电刺激伏核模型,其中DBS组大鼠进行伏核电刺激。取各组大鼠伏核,利用高效液相色谱-电化学检测法（HPLC-ECD）检测伏核DA含量。结果MA组大鼠伏核DA含量明显高于NS组（P〈0．01）和DBS组（P〈0．01）;ShS组大鼠伏核DA含量与MA组相比无明显差异。结论吗啡成瘾大鼠伏核DA含量增加,经过双侧伏核电刺激后DA含量降低,提示伏核电刺激对药物成瘾心理依赖的效应可能通过降低DA释放而起作用。     

ACh对正常大鼠和吗啡成瘾大鼠海马CA1区痛反应电活动的影响

目的 研究ACh对正常大鼠和吗啡成瘾大鼠海马CA1区痛兴奋神经元(pain-excitation neurons,PEN)和痛抑制神经元(pain-inhibitation neurons,PIN)电活动的影响,进一步探讨ACh对正常和吗啡成瘾状态下CA1区痛觉调制的作用及机制.方法 电刺激坐骨神经作为伤害性电刺激,在细胞外用玻璃微电极记录CA1区PEN和PIN的放电,观察ACh对正常大鼠和吗啡成瘾大鼠CA1区PEN和PIN电活动的影响.结果 伤害性刺激能够增强PEN的电活动,而减弱PIN的电活动.正常大鼠中,ACh使PEN的痛诱发放电频率降低,PIN的放电频率增加;ACh的作用在注射后4 min达到峰值.吗啡成瘾大鼠中,ACh同样也抑制了PEN的电活动,兴奋PIN的电活动,但是作用的高峰出现在注射后6min.胆碱能受体拮抗剂阿托品可阻断ACh的作用.结论 海马CA1区内的胆碱能神经元和毒蕈碱受体参与了伤害性信息的处理,并且起到了镇痛作用.吗啡成瘾可以降低CA1区痛反应神经元对伤害性刺激的敏感性.     

ACh对正常大鼠和吗啡成瘾大鼠海马CA1区痛反应电活动的影响

目的研究ACh对正常大鼠和吗啡成瘾大鼠海马CA1区痛兴奋神经元(pain-excitation neurons,PEN)和痛抑制神经元(pain-inhibitationneurons,PIN)电活动的影响,进一步探讨ACh对正常和吗啡成瘾状态下CA1区痛觉调制的作用及机制。方法电刺激坐骨神经作为伤害性电刺激,在细胞外用玻璃微电极记录CA1区PEN和PIN的放电,观察ACh对正常大鼠和吗啡成瘾大鼠CA1区PEN和PIN电活动的影响。结果伤害性刺激能够增强PEN的电活动,而减弱PIN的电活动。正常大鼠中,ACh使PEN的痛诱发放电频率降低,PIN的放电频率增加;ACh的作用在注射后4 min达到峰值。吗啡成瘾大鼠中,ACh同样也抑制了PEN的电活动,兴奋PIN的电活动,但是作用的高峰出现在注射后6min。胆碱能受体拮抗剂阿托品可阻断ACh的作用。结论海马CA1区内的胆碱能神经元和毒蕈碱受体参与了伤害性信息的处理,并且起到了镇痛作用。吗啡成瘾可以降低CA1区痛反应神经元对伤害性刺激的敏感性。     

脑深部电刺激对吗啡心理依赖大鼠伏核多巴胺受体的影响

目的探讨脑深部电刺激(DBS)对大鼠双侧伏核多巴胺D1A受体(D1AR)和D2受体(D2R)表达的影响以及多巴胺受体(DAR)在DBS治疗吗啡心理依赖中的作用。方法将60只SD大鼠随机分为假刺激组(ShS组)、电刺激组(DBS组)和生理盐水对照组(NS组),20只/组。用免疫组化法和RT-PCR法检测各组大鼠伏核多巴胺D1AR和D2R表达的变化。结果ShS组伏核D1AR阳性细胞数较NS组、DBS组明显增多(P0.01),而DBS组与NS组比较,差异无统计学意义(P0.05);三组间D1ARmRNA比较,差异无统计学意义(P0.05)。DBS组大鼠D2R阳性细胞数较NS组明显下降(P0.01),但较ShS组明显上升(P0.01);ShS组大鼠伏核D2RmRNA较NS组及DBS组显著上升(P0.01),而DBS组与NS组比较,差异无统计学意义(P0.05)。结论DBS对吗啡心理依赖大鼠伏核D1AR和D2R的表达起反向调节作用。     

大鼠尾核内一氧化氮对apelin受体mRNA表达的影响(英文)

目的研究大鼠尾核内一氧化氮(nitric oxide,NO)的作用机理及其与apelin 受体mRNA表达的相关性。方法大鼠尾核内微量注射NO前体L-精氨酸(L-Arg)、NG-硝基-L-精氨酸甲酯(NG-nitro-L-arginine methyl ester,L-NAME)和生理盐水(NS),应用逆转录 - 聚合酶链反应(RT-PCR)检测大鼠尾核给药 4、8、12、24 及 48 h 后一氧化氮合酶(neuronal nitric oxide synthase,nNOS) mRNA和apelin受体mRNA表达的变化及二者的相关性。结果注射L-Arg后大鼠尾核nNOS和apelin受体的mRNA表达明显升高,注射L-NAME后大鼠尾核nNOS和apelin受体mRNA表达明显降低,且均有统计学意义。注射L-Arg和L-NAME后,nNOSmRNA和apelin受体mRNA的表达呈正相关。结论在中枢神经系统,尤其是在尾核中,NOS的活性是NO作为神经递质或调质参与包括中枢痛觉调制作用在内的多种生物学作用的关键因素之一,尾核内NO的神经生物学作用可能与apelin受体作用相关 。     

吗啡成瘾对大鼠伏隔核神经元自发放电的影响

目的 研究吗啡成瘾对大鼠伏隔核电生理的影响及静脉吗啡注射对吗啡成瘾大鼠伏隔核神经元自发放电的影响探讨伏隔核在吗啡成瘾过程中的作用.方法 通过连续14日递增腹腔吗啡注射,建立急性大鼠吗啡成瘾模型,通过玻璃微电极记录吗啡依赖大鼠伏隔核单细胞细胞外放电,观察吗啡成瘾及静脉注射吗啡对大鼠伏隔核神经元放电的影响.结果 与生理盐水组相比,吗啡依赖组大鼠伏隔核神经元单位自发放电的频率分布组间差异显著(P<0.05),放电形式无明显差异.吗啡依赖大鼠伏隔核神经元放电频率静脉注射吗啡前为14.40±4.92Hz,静脉注射吗啡后降为4.10±2.65Hz.结论 吗啡成瘾对大鼠伏隔核神经元自发放电有影响,吗啡可以显著抑制吗啡成瘾大鼠的伏隔核神经元放电,伏隔核在吗啡成瘾过程具有重要作用.     

四氢原小檗碱对吗啡依赖大鼠脑内相关核团多巴胺D1、D2受体基因表达的影响

目的 研究吗啡依赖对大鼠中脑边缘多巴胺(DA)系统内相关核团DA受体的影响及四氢原小檗碱(THPB)对其的效应。方法 将30只SD大鼠随机分为5组,每组6只。正常对照组始终给予等量生理盐水腹腔注射,4组建立吗啡依赖模型。以5 mg/kg开始腹腔注射,2次/d,每次递增5 mg,一直增至第10天每次50 mg/kg;第11天起对其中的两组分别注射生理盐水12 d(Mor NS12组)和30 d(Mor NS30组),另两组分别注射30 mg/kg THPB 12 d(Mor THPB 12组)和30 d(Mor THPB 30组)。分别测定中脑腹侧被盖区(VTA)等脑结构酪氨酸单氧化酶(TM)免疫阳性神经元的平均吸光度(A)值、D1R mRNA和D2R mRNA水平。结果 与正常对照组相比,Mor NS组大鼠VTA的TM表达持续增高(P<0.01)。治疗12 d时,Mor NS12组D1R mRNA在伏隔核、杏仁核、尾壳核、前额叶皮质的含量和D3R mRNA在VTA、尾壳核、伏隔核的含量均低于正常对照组(P<0.01),而Mor THPB12组在伏隔核、杏仁核、尾壳核的D1R mRNA含量和VTA、尾壳核的D2R mRNA的含量与正常对照组的差异无显著性。治疗30 d时,Mor NS30组D1R mRNA(除杏仁核外)和D2R mRNA在各脑区的含量仍低于正常对照组(P<0.01);而Mor THPB30组D1R mRNA除前额叶皮质外的含量和D2R mRNA的含量已至正常水平。结论 THPB能抑制阿片依赖状态下VTA的TM免疫     

多巴胺系统和酒精依赖(英文)

酒精依赖是一种常见的精神疾病,社会危害大,疾病负担重。目前致力于酒精依赖的预防和治疗的研究取得的成果比较有限。为了进一步完善酒精依赖的治疗和预防措施,有必要对酒精依赖潜在的生物学机制进行深入探究。迄今为止,针对酒精依赖错综复杂的病因学的研究,大部分聚焦于多巴胺系统的关键作用。本综述总结了目前国内外对饮酒行为与多巴胺能系统之间关系的研究,发现研究结果并不一致,甚至相互矛盾,可能是由于方法学的差异、非线性的剂量效应、样本的选取差异以及多巴胺系统与其它神经递质系统之间可能存在交互作用等因素造成。     

Changes in dopamine and DOPAC following systemic administration of apomorphine and 3,4-dihydroxyphenylamino-2-imidazoline (DPI) in rats

Rats were injected systemically with either saline, apomorphine, or one of four doses of DPI (3,4-dihydroxyphenylamino-2-imidazoline) and the levels of dopamine and DOPAC determined in the nucleus accumbens and the caudate regions. DPI reduced dopamine and DOPAC levels in the nucleus accumbens, while apomorphine did not. On the other hand, apomorphine reduced the levels of dopamine and DOPAC in the caudate but not the nucleus accumbens. DPI largely was without effect in the caudate. The results are discussed in terms of possible specificity of the two dopamine agonists in the two forebrain regions.     

Differential effects of morphine, dopamine and prolactin administered iontophoretically on arcuate-ventromedial hypothalamic neurons

After induction of an experimental knee joint inflammation, the activity of single Group III and IV afferent units in the medial articular nerve of the cat was recorded at rest and during passive movements. The properties of these units were compared to those sampled from normal knee joints. The proportion of units displaying resting discharges was higher in the inflamed group. The frequency of discharges was also higher. The receptive fields were larger than those in the control units. Passive movements in the normal working range of the joint activated many more units in the inflamed joint than in the control sample. We conclude that joint inflammation sensitizes articular nociceptors to be active not only at rest, but also during normally innocuous joint movements.     

Real-time measurement of dopamine release in rat brain

Dopamine release at the submicromolar level has been observed in the striatum of an anesthetized rat on a millisecond time scale. Fast-scan cyclic voltammetry with Nafion-coated microelectrodes has been synchronized with electrical stimulation of the medial forebrain bundle, and synaptic overflow is observed following a burst of 15 impulses. The rapid appearance of dopamine following this stimulus indicates that the source of dopamine is very close (approximately 10 micron) to the electrode. The rapid disappearance of released dopamine reflects the potency of cellular uptake for dopamine. Inhibition of dopamine uptake with nomifensine allows the measurement of dopamine overflow as a result of a single stimulus impulse or with low-frequency stimulations, both comparable to physiological dopaminergic impulse flow.     

Iontophoretically applied dopamine depolarizes and hyperpolarizes the membrane of cat caudate neurons

Dopamine (DA) was applied iontophoretically on intracellularly recorded cat caudate neurons. Ejected approximately 100 μm away from the cell soma, it caused slow depolarizations of the membrane while the ongoing firing rate was reduced. This last effect was not due to sodium inactivation. Cortically evoked EPSP-IPSP sequences were inhibited during the depolarizations. The latency of cortically evoked action potentials was consistently increased during DA-ejections. These effects were blocked by fluphenazine, a relatively selective blocker of the DA-sensitive adenylate cyclase. Nevertheless, there are serious doubts as to the specificity of these actions of DA as a number of other substances like naloxone, nicotine, acetylcholine or glutamate-diethylester occasionally had very similar effects on membrane potential, firing rate and cortically evoked EPSP-IPSP sequences.If DA was applied nearer to the soma, approximately 50 μm away, 70% of the recorded neurons continued to display the slow depolarizations above described, while 30% of the cells now reacted by a hyperpolarization accompanied also by a reduced firing rate. If DA was applied for prolonged periods on such cells, the initial hyperpolarization was followed by the slow depolarization.The observation that during the slow depolarization there is a decrease in firing rate and amplitude of the cortically evoked IPSP is explained by the assumption that the region of the axon hillock is hyperpolarized by DA, and that the slow depolarization is a phenomenon restricted to the distant recording site and possibly to the dendritic region.None of the 74 responsive neurons displayed an increased firing rate when DA was ejected either continously, i.e. for more than 5 sec, or in short pulses of 50–500 msec.     

Differential effects of dopamine agonists on acoustically and electrically elicited startle response: Comparison to effects of strychnine

This study sought to determine where drugs that are known to alter sensorimotor reactivity measured with the acoustic startle reflex ultimately act within the acoustic startle pathway. To do this, startle was elicited either acoustically or electrically within various nuclei believed to comprise the acoustic startle pathway. Direct infusion of serotonin into the subarachnoid space of the lumbar spinal cord increased acoustic startle and startle elicited electrically through the ventral cochlear nucleus (VCN) to a comparable degree. Subconvulsant doses of strychnine increased startle elicited acoustically or electrically through either the VCN or the nucleus reticularis pontis caudalis (RPC), pointing to spinal locus of action of strychnine after systemic administration. In marked contrast, the dopamine agonists d-amphetamine and apomorphine consistently increased acoustic startle but actually depressed startle elicited electrically through the VCN or the RPC. These later results suggest that dopamine agonists increase sensorimotor reactivity measured with acoustic startle by acting on sensory rather than motor parts of the reflex arc.