用脉冲伏安法观察多巴胺D1D2受体拮抗剂对大鼠纹体中DOPAC...

Dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) was detected by differential normal pulse voltammetry (DNPV) in chloral hydrate anesthetized rat striatum. The effects of some dopamine D-1 and D-2 antagonists on DOPAC concentration were observed in order to demonstrate the role of presynaptic D-1 and D-2 receptors in the feedback of dopamine synthesis and metabolism. The results showed that the mixed antagonists haloperidol (0.5 mg/kg s.c.) and chlorpromazine (5 mg/kg s.c.), the selective D-1 antagonist SCH23390 (1 mg/kg s.c.), and the selective D-2 antagonist sulpiride (5 mg/kg s.c.) all increased DOPAC concentration significantly. The percentages of increase were 140%, 102%, 26% and 40% in comparison with basal DOPAC concentration (14 +/- 2 mumol/L), respectively. These results indicate that not only presynaptic D-2 receptor regulates DA synthesis and metabolism, but that the presynaptic D-1 receptor also takes part in this feedback mechanism.     

两种吗啡依赖大鼠模型脑内单胺神经递质水平的比较

目的 通过对吗啡诱导的躯体依赖与精神依赖两种大鼠模型脑内单胺类递质水平的比较,探讨其在吗啡依赖形成中的作用.方法 采用剂量递增法复制吗啡依赖大鼠模型,然后用纳洛酮催促,引起躯体戒断症状.连续给予吗啡 (5 mg/kg,ip) 6 d,引起大鼠产生显著的条件性位置偏爱效应.脑组织去甲肾上腺素(NE)、5-羟色胺(5-HT)和多巴胺(DA)含量采用荧光分光光度法测定.结果 吗啡依赖大鼠催促戒断后脑内NE和5-HT水平明显升高,DA水平下降.吗啡在引起大鼠明显位置偏爱的同时,使大鼠脑内DA和5-HT水平显著升高,NE无明显改变.结论 吗啡依赖的形成和戒断与脑内单胺神经递质有密切关系,吗啡依赖的躯体戒断症状与NE升高有关,而吗啡诱导的精神依赖则与脑内DA水平升高有关.     

5-羟色胺受体在帕金森病治疗中的应用前景

帕金森病(Parkinson's disease,PD)是世界上常见的神经退行性疾病,严重危害中老年人健康,给家庭和社会带来沉重负担.PD的病理学特征为黑质纹状体内多巴胺含量减少,进而导致运动迟缓和肌强直等运动症状,但PD的发病机制尚不明确.研究表明5-羟色胺(5-HT)受体可能参与PD的发病机制.本文回顾5-HT受体...     

Effect of PD Ⅰ Administration on Dopamine Receptors mRNAs Expression in the Lesioned Striatum of PD Rat Model

To study the effect of PD Ⅰ administration on dopamine receptors （DR, , DRz ） mRNAs expression in the lesioned striatum of the PD rat model and confirm if PDⅠ has the effect of dopamine receptor agonist. The PD rats with unilateral 6-hydroxydopamine lesioned were administrated with PD Ⅰ , L-dopa methyl/benserazide, L-dopa methyl/benserazide/ PD Ⅰ , normal saline respectively for 4 weeks and their behavioral changes were observed. Then the rats were sacrificed and RT-PCR technique was used to detect changes of dopamine receptors （DR1, DR2） mRNAs expression in the ipsilateral striatum 1 day after the last treatment. The results showed that treatment with PD Ⅰ plus L-dopa resulted in a stable contralateral rotation behavior; treatment with L-dopa resulted in a progressively increased contralateral rotation behavior. Rotation behavior induced by anhydromorphine decreased with PD Ⅰ or PD Ⅰ plus L-dopa treatment. Treatment With L-dopa or PD Ⅰ plus L-dopa, up-regulation of DR, mRNA and down-regulation of DR2 mRNA were observed in the ipsilateral striatum which were more obvious than that treated with PD Ⅰ or vehicle （P〈0. 05）. It was concluded that long-term treatment with PD Ⅰ could alleviate the behavior of PD rats. PD Ⅰ had no apparent effect on the dopamine receptors （DRI , DRz ） mRNAs expression in the ipsilateral striatum and the PD Ⅰ has no agonist effect on dopamine receptors.     

惊厥大鼠不同脑区突触体内单胺类递质水平的动态变化及意义

目的 探讨单胺类递质与惊厥的关系.方法 选用Wistar大鼠32只,采用腹腔注射硫代氨基脲制作惊厥模型.取大脑皮层、海马、纹状体三个脑区,制备出突触小体.用荧光分光光度计测定五羟色胺(5-HT)、多巴胺(DA)、去甲肾上腺素(NA)三种单胺类递质的含量.结果 5-HT含量在惊厥发作组中,大脑皮层和海马区显著下降(P<0.01),而纹状体仅致死组有明显降低(P<0.01);DA含量在惊厥组中仅纹状体有显著下降(P<0.01);而大脑皮层和海马区无明显变化(P>0.05);NA含量在惊厥组中,仅海马区有明显下降(P<0.01);而大脑皮层则随惊厥初发、再发和致死组反见升高;在纹状体,致死组有明显下降(P<0.05).结论 惊厥的发生、发展与特定脑区突触体内特定的单胺类递质含量有关,并非所有脑区突触体内出现普遍性单胺类递质的下降;不同部位的神经递质与惊厥的敏感性和发作严重程度有关.     

Effects of phentolamine and propranolol on the changes of pain threshold and contents of MEK and LEK in rat brain after EA

The contents of Met-enkephalin (MEK) and Leu-enkephalin (LEK) in striatum and MEK in hypothalamus of rat increased markedly after electroacupuncture analgesia (EAA). Intraperitoneal injection of phentolamine, a blocker of alpha receptor, potentiated the EAA and abolished the effects of EA increasing MEK and LEK contents; while injection of propranolol, a blocker of beta receptor, partially inhibited the EAA, as well as abolished the effects of EA increasing MEK and LEK concentrations in the striatum and the hypothalamus, and also elevated the MEK and LEK contents in hippocampus and MEK level in cortex. The results indicate that EA regulates metabolism of MEK and LEK, as well as EAA partially via alpha and beta receptors.     

生理因素对纹状体多巴胺D2受体表达的影响

为了研究大鼠的品系、性别和年龄相关的体重因素对纹状体多巴胺D2受体表达的影响,用大鼠纹状体和125I-IBZM{(S)-3-碘-2-羟基-6-甲氧基-N-[(1-乙基-2-吡咯烷基)甲基]苯甲酰胺}结合,按照大鼠的品系、性别和年龄相关的体重进行组间配对比较.结果:大鼠的品系和性别对纹状体多巴胺D2受体的125I-IBZM结合无明显影响,但纹状体多巴胺D2受体的125I-IBZM结合却有体重相关性的减少.由此表明,纹状体多巴胺D2受体可能具有年龄依赖性的减少.因此,在临床研究中严格的年龄配对是必须的.     

生理因素对纹状体多巴胺D2受体表达的影响

为了研究大鼠的品系，和年龄相关的体重因素对纹状体多巴胺Ｄ２受体表达的影响，用大鼠纹状体和＾１、２５Ｉ－ＩＢＺＭ｛（Ｓ）－３－碘－２－羟基－６－甲氧基－Ｎ－「（１－乙基－２－吡咯烷基）甲基」苯甲酰胺｝结合，按照大鼠的品系，性别和年龄相关的体重进行组间配对比较。结果；大鼠的品系和性别对纹状体多巴胺Ｄ２受体的＾１２５Ｉ－ＩＢＺＭ结合无明显影响，但纹状体多巴胺Ｄ２受体的＾１２５Ｉ－ＩＢＺＭ结合却有体重相关     

Mechanisms and innovations: Pharmacologic mechanisms of crystal meth

Crystal meth is a form of the stimulant drug methamphetamine that, when smoked, can rapidly achieve high concentrations in the brain. Methamphetamine causes the release of the neurotransmitters dopamine, norepinephrine and serotonin and activates the cardiovascular and central nervous systems. The levels of dopamine are low in the brain of some drug users, but whether this represents neuronal loss is uncertain. The areas of the brain involved in methamphetamine addiction are unknown but probably include the dopamine-rich striatum and regions that interact with the striatum. There is no medication approved for the treatment of relapses of methamphetamine addiction; however, potential therapeutic agents targeted to dopamine and nondopamine (e.g., opioid) systems are in clinical testing.