大鼠伏膈核内多巴胺受体与电针镇痛的关系

目的：研究多巴胺受体拮抗剂左旋四氢巴马汀（ｌ－ＴＨＰ）加强电针镇痛（ＥＡＡ）的原理，阐明中枢神经系统内多巴胺（ＤＡ）系统在ＥＡＡ中的作用，方法：分别将Ｄ１受激动剂ＳＫ＆Ｆ－３８３９３和Ｄ２受体激动剂ｑｕｉｎｐｉｒｏｌｅｈｙｄｒｏｃｈｌｏｒｉｄｅ（Ｑｕｉ）注射入大鼠伏膈核，观察对ＥＡＡ及ｌ－ＴＨＰ加强ＥＡＡ的作用。结果：ＳＫ＆Ｆ－３８３９３（５μｇ，１０μｇ）明显对抗ｌ－ＴＨＰ加强ＥＡＡ的作用，１０     

Enhancement of (-)-stepholidine on protein phosphorylation of adopamineand cAMP-regulated phosphoprotein in denervated striatum of oxidopaminelesioned rats

目的：研究左旋千金藤立定（ＳＰＤ）对羟多巴胺损毁大鼠纹状体中ＤＡＲＰＰ３２蛋白磷酸化程度的影响．方法：反磷酸化测定脱磷ＤＡＲＰＰ３２的含量．结果：ＳＰＤ不改变正常大鼠纹状体中ＤＡＲＰＰ３２磷酸化的程度，但能拮抗Ｄ１激动剂的作用；对羟多巴胺损毁大鼠的损侧纹状体，ＳＰＤ使脱磷ＤＡＲＰＰ３２的含量降低４４％，给予Ｄ１拮抗剂可以拮抗这一作用．结论：在损侧纹状体，ＳＰＤ显示Ｄ１激动剂的作用特性，增加ＤＡＲＰＰ３２蛋白的磷酸化，而在正常纹状体，ＳＰＤ表现为Ｄ１拮抗剂．     

Effects of tetrahydroprotoberberines on dopamine D_2 receptors in ventral tegmental area of rat

阐明四氢原小檗碱同类物（ＴＨＰＢ）对大鼠中脑腹侧被盖区（ＶＴＡ）多巴胺（ＤＡ）受体的作用特性，并比较它们的作用强度．方法：采用大鼠在体胞外单位放电记录．结果：观察了１１个ＴＨＰＢ均可完全地翻转ＤＡ受体激动剂阿扑吗啡（２０μｇ·ｋｇ－１）所产生的放电抑制作用，为Ｄ２受体拮抗剂的作用特性．ＴＨＰＢ对Ｄ２受体的作用与Ｃ２位上的ＯＨ基团有密切的关系．它们的作用强度（ＥＤ５０，μｇ·ｋｇ－１）：ＴＨＰＢ１４３（５６）＞ＳＰＤ（８５）＞Ｉｓｏ（１７０）＞ＴＨＰ（３３）＞ＴＨＢ（４８）＞ＴＨＰＢ１８（６６）＞ＴＨＰＢ１（１７９）＞ＴＨＰＢ１９（４０８）＞ＴＨＰＢ１２６（５１０）＞ＴＨＰＢ１０４（１０１９）＞ＴＨＰＢ１０（４８１５）．结论：１１个ＴＨＰＢ均为ＶＴＡＤ２受体拮抗剂，以Ｃ２位上有ＯＨ基团的ＴＨＰＢ１４３作用最强．     

左旋千金藤立定增强K~ 去极化对大鼠纹状体酪氨酸3-单加氧酶的激活作用(英文)

目的：研究Ｋ＋去极化对大鼠纹状体突触体酪氨酸３单加氧酶（ＴＭ）激活的机制及ＳＰＤ对此激活的影响．方法：应用ＨＰＬＣＥＣＤ法测定ＤＯＰＡ为ＴＭ的活性，并应用同位素法测定ＰＫⅡ和ＰＫＣ的活性．结果：ＳＰＤ１，１０和１００μｍｏｌ·Ｌ－１增强Ｋ＋去极化对突触体ＴＭ的活性，ＰＫＣ抑制剂ＰＭＢ１０μｍｏｌ·Ｌ－１能完全逆转Ｋ＋去极化的激活效应，而选择性Ｄ２受体激动剂ＱＰ，ＣａＭ拮抗剂Ｗ７和去除反应液中的Ｃａ２＋均不影响Ｋ＋去极化对ＴＭ的激活．Ｋ＋去极化使突触体ＰＫＣ的活性增加５３％，而对ＰＫⅡ的活性无影响．ＳＰＤ和ＱＰ均不影响Ｋ＋去极化对ＰＫＣ的激活．结论：Ｋ＋去极化对突触体ＴＭ的激活作用是由ＰＫＣ介导的，不受突触前ＤＡ自身受体的调控，但被ＳＰＤ增强．     

左旋千金藤啶碱对外周血管多巴胺DA1和DA2受体亚型的作用

用家兔离体血管环方法,研究左旋千金藤啶碱(l-SPD)对外周血管DA₁和DA₂受体亚型的作用。结果表明,l-SPD使DA₁受体激动剂FODA诱发的肾、肺和肠动脉以及DA₂受体激动剂PBDA诱发的肠和股动脉舒张反应的量效曲线非平行右移,最大反应(Emax)降低,均呈非竞争性拮抗;l-SPD本身还可使肾和肺血管产生轻度的浓度依赖性舒张反应,表现为DA₁受体激动剂的作用特性。提示l-SPD为外周血管DA₁和DA₂受体的混合性阻滞剂并兼有DA₁受体部分激动剂的双重作用特性。     

Effects of long-term application of dopamine HCl on dopamine agonist-induced cAMP production in rat renal cortex

目的：观察长期给予盐酸多巴胺对大鼠肾皮质多巴胺受体亚型所介导的腺苷酸环化酶活性的影响．方法：用放免分析法测定ｃＡＭＰ含量，作为反映多巴胺受体功能的指标．结果：长期给予盐酸多巴胺可显著减少肾皮质由非诺多泮引起的ｃＡＭＰ增加的量和在Ｓｃｈ２３３９０存在下由ＰＢＤＡ引起的ｃＡＭＰ降低的量，但其变量百分比则与对照组无显著差异．Ｓｃｈ２３３９０可阻断由非诺多泮和ＰＢＤＡ引起的ｃＡＭＰ的增加，而多潘立酮可阻断在Ｓｃｈ２３３９０存在下由ＰＢＤＡ引起的ｃＡＭＰ的降低．结论：长期应用多巴胺可使大鼠肾皮质的ＤＡ１和ＤＡ２受体均发生明显的“下调”，但余留受体的反应性不变．     

M_1，M_2受体激动剂和阻滞剂对犬呼吸的影响

目的：研究Ｍ１和Ｍ２受体激动剂和阻滞剂对犬呼吸的影响．方法：用ＲＭ８６多导生理记录仪通过胸带式呼吸换能器测定ＲＲ，ＴＶ和ＭＶＶ，并取动脉血测ｐＯ２，ｐＣＯ２和ｐＨ．结果：发现Ｍ１Ｒ激动剂Ｐｉｌ和Ｍ２Ｒ激动剂６βＡＮｉｖ或椎动脉给药分别产生呼吸兴奋和抑制，ＲＲ，ＭＶＶ增高或降低（Ｐ＜００５），血气亦出现相应变化．Ｍ１Ｒ阻滞剂Ｐｉｒ，Ｓｃｏ和Ｍ２Ｒ阻滞剂ＡＦＤＸ１１６，Ａｔｒ分别拮抗甚至翻转Ｐｉｌ的呼吸兴奋和６βＡＮ的呼吸抑制作用．结论：激动呼吸中枢Ｍ１Ｒ呼吸兴奋，激动呼吸中枢Ｍ２Ｒ呼吸抑制，阻断之则作用相反．     

慢性给予左旋千金藤立定对纹状体多巴胺D1和D2受体密度和更新…

目的：观察慢性给予左旋千金藤立定（ＳＰＤ）对纹状体多巴胺（ＤＡ）受体密度和更新率的影响，推论ＳＰＤ的药理性质。方法：应用ＥＥＤＱ失活ＤＡ受体，用放射受体结合分析法测定受体的密度，计算有关的动力学参数。结果：慢性给予ＳＰＤ２１ｄ便纹状体Ｄ１与Ｄ２受体密度分别增加４１．５％和４３．７％。并且慢性给予ＳＰＤ改变ＤＡ受体的更新率，使Ｄ１受体的生成速度由对照组的１．７７ｐｍｏｌ·ｈ＾－１／ｇ ｐｒｏｔｅｉｎ     

治疗偏头痛药物与5—HT受体

偏头痛发病部位在脑膜血管上，５－ＨＴ系统参与首要作用，多巴胺（ＤＡ）系统居其次。急性发作前期释放大量５－ＨＴ，作用于脑膜血管，使血管收缩；急性发作时，血管过度舒张，浆液外渗，形成无菌性炎症，刺激冲动从三叉神经上传，出现恶心、呕吐、头痛、怕光等神经症状。偏头痛发作时，ＤＡ系统处于超敏。发作期应用５－ＨＴ１Ｄ受体激动剂和Ｄ２受体拮抗剂治疗；长期性预防发作可用５－ＨＴ２受体拮抗剂和ＤＡ受体激动剂。舒马曲     

三种阿片受体激动剂对突触传递的抑制作用

目的：比较不同浓度三种阿片受体激动剂对突触传递的抑制作用．方法：用细胞内记录和细胞外微电泳技术，于大鼠伏核脑片制备上记录神经元的兴奋性突触后电位和谷氨酸钠所致细胞膜去极化．结果：（ＤＡｌａ２，ＮＭｅＰｈｅ４，Ｇｌｙｏｌ）ｅｎｋｅｐｈａｌｉｎ（ＤＡＧＯ），（ＤＰｅｎ２，５）ｅｎｋｅｐｈａｌｉｎ（ＤＰＥＮ），ａｎｄｔｒａｎｓ（±）３，４ｄｉｃｈｌｏｒｏＮｍｅｔｈｙｌＮ［２（１ｐｙｒｏｌｉｄｉｎｙｌ）ｃｙｃｌｏｈｅｘｙｌ］ｂｅｎｚｅｎｅａｃｅｔａｍｉｄｅｍｅｔｈａｎｅｓｕｌｆｏｎａｔｅ（Ｕ５０４８８Ｈ）（１μｍｏｌ·Ｌ－１）均降低突触传递，尤以ＤＡＧＯ抑制作用最著．结论：三种阿片受体激动剂对突触传递的抑制作用均具有浓度依赖性，其作用机制与谷氨酸介导的突触传递受抑制有关．     

Role of DA in the stimulant effect of DITA in mice; comparison with d-amphetamine.

The effect of DL-alpha methyltyrosine (alpha-MT), 6-hydroxydopa (6-OH DOPA), haloperidol, phenoxybenzamine and propranolol on the stimulant activity of the anorexigenic agents (3',4'-dichloro-2-(2-imidazolin-2-yl-thio)-acetophenone HBr) (DITA) and d-amphetamine was studied in male mice. The pretreatment of mice with alpha-MT, (32, 64 mg/kg i.p.), significantly reduced the increase in motor activity induced by DITA or d-amphetamine. On the other hand, pretreatment of mice with 6-OH DOPA, (100, 150 mg/kg, i.v.), did not significantly after the stimulant effect of either DITA or d-amphetamine. In the case of haloperidol, it significantly reduced the increase of motor activity induced by DITA or d-amphetamine; propranolol and phenoxybenzamine were ineffective. Our results support the hypothesis that the stimulant effect of DITA and d-amphetamine depends mainly on the integrity of the central dopaminergic rather than the noradrenergic system.     

生长抑素联合小剂量多巴胺辅助治疗上消化道大出血临床分析

目的探讨生长抑素联合小剂量多巴胺辅助治疗上消化道大出血临床效果及机制。方法将60例上消化道大出血患者随机分为治疗组(30例)和对照组(30例),两组均给予相同的补液、止血、禁食水、胃肠减压等基础治疗,治疗组加用生长抑素联合小剂量多巴胺,观察记录两组患者治疗效果与肝肾功能的变化。结果治疗组有效率93.3%,对照组有效率86.7%,治疗组有效率高于对照组(P<0.05),治疗组患者治疗1周后肝肾功能优于对照组,差异具有统计学意义(P<0.05)。结论生长抑素联合小剂量多巴胺辅助治疗上消化道出血,能提高有效率,保护患者肝肾功能,具有较好的辅助治疗作用。     

Differential effects of amphetamine isomers on SN self-stimulation: Evidence for DA neuron subtypes

The present experiment investigated the effects of varying doses of D- and L-amphetamine on intracranial self-stimulation (ICSS) in the medial or lateral substantia nigra (SN). It was found that the effects of D- and L-amphetamine on ICSS in the SN differ in these two sites. In the medial SN, there were no significant differences between the effects of D- and L-amphetamine on ICSS at any of the doses tested. Both isomers moderately facilitated ICSS with the peak effect at 0.8 to 2.0 mg/kg. By contrast, in the lateral SN, D-amphetamine produced a strong dose-dependent facilitation of ICSS which peaked at 2 mg/kg while L-amphetamine was ineffective below 7 mg/kg. Above 7 mg/kg L-amphetamine increased ICSS rates. The present experiments suggest that the medial and lateral SN are functionally different with respect to ICSS. The possibility that the present medial-lateral SN differences are mediated by two different types of dopamine cells is discussed. In addition, the effects of D- and L-amphetamine on ICSS in the lateral hypothalamus are discussed in light of the present findings.     

Postsynaptic dopamine (DA) receptor stimulator properties of the putative DA autoreceptor-selective agonist B-HT 920 uncovered by co-treatment with the D-1 agonist SK&F 38393

Postsynaptic dopaminergic behavioural effects of D-2 agonists can be promoted by concomitant D-1 receptor activation. The present experiment explored whether such effects could be elicited by the putative autoreceptor-selective D-2 agonist B-HT 920, when combined with the D-1 agonist SK&F 38393. Except for occasional jerks induced by B-HT 920, neither agonist caused significant dopaminergic stimulation when given separately, whereas combined treatment with SK&F 38393 and B-HT 920 induced clear-cut motor activation — particularly focused stereotyped licking and sniffing — in reserpine/AMT-pretreated rats. Both the D-1 antagonist SCH 23390 and the D-2 antagonist spiperone abolished these effects, while the SK&F/B-HT-induced stimulation was not significantly affected by the alpha₂-blocker idazoxan. It appears that classical postsynaptic DA receptor-stimulatory properties of B-HT 920 can indeed be demonstrated, provided that sufficient D-1 receptor tone prevails.     

The potential role of dopamine D3 receptor neurotransmission in cognition

Currently available treatments have limited pro-cognitive effects for neuropsychiatric disorders, such as schizophrenia, Parkinson's disease and Alzheimer's disease. The primary objective of this work is to review the literature on the role of dopamine D₃ receptors in cognition, and propose dopamine D₃ receptor antagonists as possible cognitive enhancers for neuropsychiatric disorders. A literature search was performed to identify animal and human studies on D₃ receptors and cognition using PubMed, MEDLINE and EMBASE. The search terms included “dopamine D₃ receptor” and “cognition”. The literature search identified 164 articles. The results revealed: (1) D₃ receptors are associated with cognitive functioning in both healthy individuals and those with neuropsychiatric disorders; (2) D₃ receptor blockade appears to enhance while D₃ receptor agonism seems to impair cognitive function, including memory, attention, learning, processing speed, social recognition and executive function independent of age; and (3) D₃ receptor antagonists may exert their pro-cognitive effect by enhancing the release of acetylcholine in the prefrontal cortex, disinhibiting the activity of dopamine neurons projecting to the nucleus accumbens or prefrontal cortex, or activating CREB signaling in the hippocampus. These findings suggest that D₃ receptor blockade may enhance cognitive performance in healthy individuals and treat cognitive dysfunction in individuals with a neuropsychiatric disorder. Clinical trials are needed to confirm these effects.     

3H-Apomorphine interactions with dopamine receptors in calf brain

3H-apomorphine binds to membranes from areas of the corpus striatum and limbic system of calf brain saturable and with a drug specificity indicating that it labels dopamine receptors. In terms of drug specificity, log-logit displacement curve slopes and number of binding sites, 3H-apomorphine interacts with receptors in a manner more like 3H-dopamine than 3H-haloperidol. These properties of 3H-apomorphine binding are those of an apparently "pure" agonist in contrast to the partial agonist effects of apomorphine upon the dopamine-sensitive adenylate cyclase.     

莫达非尼觉醒作用机制研究进展

莫达非尼是强效促觉醒药物,主要用于治疗发作性睡病等原因引起的白天嗜睡。莫达非尼和多巴胺（dopamine,DA）转运体有一定亲和性,可增加脑内DA释放,也影响去甲肾上腺素（no-radrenaline,NA）、5-羟色胺（serotonin,5-HT）、谷氨酸、γ-氨基丁酸（-γaminobutyric acid,GA-BA）、orexin和组胺能等神经系统,但觉醒作用机制存有众多争议。行为学研究发现,DA转运体基因敲除（knock-out,KO）动物给予莫达非尼后,不能产生显著的觉醒作用;D2受体KO）动物对莫达非尼的觉醒作用显著降低,前处理D1受体拮抗剂,莫达非尼对D2受体KO小鼠的促觉醒作用消失,提示多巴胺能D1/D2受体在莫达非尼促觉醒作用中至关重要,其他神经递质的变化可能是觉醒的继发性作用。本文综述莫达非尼觉醒作用机制研究进展。     

Opposite locomotor asymmetries elicited from the medial and lateral SN by modulation of SN DA receptors

In combination with systemic d-amphetamine (1 mg/kg), apomorphine or alpha-flupenthixol were unilaterally injected into either the medial or lateral substantia nigra pars compacta (SNC) of adult male hooded rats. Direction and magnitude of circling were measured. Alpha-flupenthixol (5 and 15 micrograms) injected into the medial SNC caused rats to circle contraversive to the injected side while laterally placed injections produced ipsiversive circling. Apomorphine (5 and 15 micrograms) induced ipsiversive circling when injected into the medial SNC but had no effect in the lateral SNC. The results show that nigrostriatal mediated circling can be induced by modulation of dopamine (DA) receptors in the SNC. Furthermore, the findings support the notion that lateral SNC DA neurons are functionally antagonistic to medial SNC DA neurons with respect to circling. The results also suggest that there may be medial-lateral SNC differences in the type of DA receptors.     

Presynaptic dopamine DA2-receptors in rabbit jejunal arteries

Summary Excitatory junction potentials (e.j.ps) evoked by nerve stimulation with 15 pulses at 1 Hz were recorded from muscle cells of rabbit isolated jejunal arteries. LY 171555 1 mol/l, SKF 38393 10 mol/l, dopamine 10 ol/l and clonidine 0.1 mol/l depressed all e j.ps in the train. The percentage inhibition was inversely related to the number of pulses. S- and R-sulpiride, 10 mol/l, domperidone 1 mol/l, SCH 23390 1 mol/l and rauwolscine 1 mol/l did not change, or even depressed the first e j.ps. Of these compounds only S- and R-sulpiride, 10 mol/l and rauwolscine 1 mol/l facilitated the late e.j.ps. The percentage facilitation increased with the number of pulses until a maximum was reached; rauwolscine 1 ol/l had the largest effect. S- and R-sulpiride, 10 mol/l, as well as domperidone 1 ol/l antagonized the action of LY 171555 1 mol/l. S-Sulpiride was more potent than its R-isomer. SCH 23390 1 mol/l and rauwolscine 1 mol/l blunted the effect of SKF 38393 10 mol/l. Rauwolscine 1 mol/l slightly reduced the inhibition by dopamine 10 mol/l; S-sulpiride 10 mol/l was antagonistic only in the presence of rauwolscine 1 mol/l. When rauwolscine 1 mol/l, prazosin 0.1 mol/l, propranolol 1 mol/l and cocaine 10 mol/l was added to the medium, dopamine 10 mol/l continued to produce the same depression of e j.ps, as in the absence of these compounds. Under such conditions S-sulpiride 10 mol/l also counteracted dopamine 10 gmol/l. Rauwolscine 1 mol/l prevented the effect of clonidine 0.1 mol/l. The antagonists were not absolutely selective against only one type of agonist. We suggest that both presynaptic DA₂- and postsynaptic DA₁-receptors are present in rabbit jejunal arteries. The activation of either receptor-type may depress the e j.ps. Dopamine interferes with neuroeffector transmission due to ₂-adrenoceptor agonist properties; its DA₂-effect is unmasked only after ₂-adrenoceptor blockade. There was no evidence for a co-transmitter function of dopamine. Send offprint requests to P. Illes at the above address     

Nucleus accumbens dopamine and discriminated approach learning: interactive effects of 6-hydroxydopamine lesions and systemic apomorphine administration

RATIONALE: Drug-paired stimuli elicit drug craving and relapse in addicts and drug-seeking behavior in rats. The functional integrity of the basolateral amygdala (BLA) is necessary for reinstatement of cocaine-seeking behavior elicited by cocaine-conditioned stimuli, but not by cocaine itself. It is unclear, however, whether the BLA plays a similar role in reinstatement of heroin-seeking behavior. OBJECTIVES: To this end, we examined the effects of tetrodotoxin (TTX)-induced inactivation of the BLA on conditioned and heroin-primed reinstatement of extinguished heroin-seeking behavior. METHODS: Rats were trained to press a lever for IV infusions of heroin (maintenance dose of 25 microg/infusion) paired with presentations of a light-tone stimulus complex during daily 3-h sessions. Responding was then allowed to extinguish prior to reinstatement testing. Reinstatement of extinguished heroin-seeking behavior (i.e. lever pressing in the absence of heroin reinforcement) was measured in the presence of response-contingent presentation of the heroin-paired stimulus complex alone and then following TTX (5 ng/0.5 microl per side) or vehicle infused into the BLA. In a separate group of rats, reinstatement was measured after saline injection (SC) and then following heroin priming (0.25 mg/kg, SC) with TTX or vehicle infused into the BLA. RESULTS: Both response contingent presentation of the stimulus complex and heroin priming significantly reinstated extinguished heroin-seeking behavior, and BLA inactivation abolished the ability of the heroin-paired stimuli and of heroin priming to reinstate responding. CONCLUSIONS: These findings suggests that the BLA is a critical component of the neural circuitry that mediates conditioned and heroin-induced reinstatement of heroin-seeking behavior. Furthermore, different neural substrates may mediate drug-primed relapse to cocaine versus heroin-seeking behavior.