钙成像研究左旋千金藤啶碱（SPD），氟哌啶醇（HAL），氯氮平（CLO）对NMDA受体两种亚型（NR1a／NR2A，NR1a／NR2B）作用

目的：已有研究表明精神分裂症与脑内NMDA受体功能有关。经典安定剂HAL和非经典安定剂CLO均能抑制NMDA受体电流。初步临床研究表明SPD有抗精神分裂症的作用，并且具有非经典安定剂的特性。本实验旨在运用钙成像技术研究SPD是否也与HAL，CLO作用相同，能抑制NMDA受体介导的电流。方法：在HEK293     

氯代斯阔任对多巴胺受体的作用

目的:比较四氢原小檗碱同类物(THPB)和氢化苄基-四氢异喹啉类(HBTI)两类化合物对DA受体的作用强度,从而找出对DA受体作用更有效的化合物。方法:用小牛纹状体膜蛋白对D_1和D_2受体进行放射受体结合分析并进行大鼠行为实验。结果:(±)12-氯代斯阔任(CSL)对D_1和D_2受体的亲和力分别为13和51nmol·L~(-1),与先导化合物左旋千金藤立定[(-)stepholidine,SPD]在同一水平,动物行为实验表明它对DA受体有阻滞作用,但在超敏条件下,出现激动作用,这些特点与SPD的作用类似。结论:CSL是目前THPB中对DA受体作用最强者,与SPD类似是对DA受体阻滞剂兼有激动作用。     

白茅根多糖对小鼠耐缺氧作用的影响

目的观察白茅根多糖(RIP)对小鼠耐缺氧作用的影响,为白茅根的临床应用和药物开发研究提供一定理论依据.方法超声提取RIP.60只小鼠随机分为6组,分别灌胃给予生理盐水、普萘洛尔和不同剂量的RIP,观察小鼠缺氧存活时间和耗氧量.结果灌胃给予RIP 50,100,200,400 mg·kg-1和普萘洛尔20 mg·kg-1,使小鼠0～5 min的耗氧量分别降低2.48%,23.14%,10.74%,5.79%和28.93%,5～10 min的耗氧量分别降低21.13%,16.90%,38.73%和9.86%.灌胃给予氯化钠注射液、普萘洛尔20 mg/kg和RIP 50,100,200,400 mg·kg-1,小鼠缺氧30 min存活率分别为0,0,20%,10%,50%,20%.普萘洛尔组、RIP 200 mg·kg-1和400 mg·kg-1组,小鼠的缺氧存活时间分别延长33.16%,37.31%和35.23%.结论RIP能明显增强实验小鼠的耐缺氧作用.     

碘化N-正丁基氟哌啶醇对培养大鼠心肌细胞缺氧复氧损伤及Egr-1表达的影响

目的观察碘化N-正丁基氟哌啶醇(F2)对培养大鼠心肌细胞缺氧复氧(H/R)所致的损伤及早期生长反应蛋白-1(Egr-1)表达变化的影响。方法制作心肌细胞H/R损伤模型。倒置显微镜和透射电子显微镜下观察心肌细胞一般形态、自发性搏动及超微结构的变化。采用免疫组织化学方法测定心肌细胞Egr-1蛋白阳性表达的细胞数。结果H/R造成心肌细胞形态异常、搏动节律紊乱,导致超微结构损害;H/R诱导心肌细胞Egr-1表达明显增强。缺氧及复氧前给予F2则能改善H/R所致心肌细胞病理损害,抑制心肌细胞Egr-1的过量表达。结论F2对培养心肌细胞H/R损伤具有保护作用,这可能与其抑制Egr-1蛋白过量表达有关。     

来复汤对小鼠耐缺氧能力的影响

来复汤为近代名医张锡纯的“救脱”常用方，为进一步探索其治疗“厥脱证”的现代药理学机制，本试验观察了该方水煎剂对小鼠常压耐缺氧能力的影响、对异丙肾上腺素处理的小鼠常压在耐缺氧能力的影响、对氰化钾中毒缺氧小鼠的影响以及对小鼠减压缺氧能力的影响，结果证实其对小鼠的上述四种耐缺氧能力均有明显的增强作用（Ｐ＜０．０５），这种作用可能是其抗休克作用的基础之一。     

左旋千金藤立定对大鼠血清中催乳素水平的影响(英文)

目的:观察左旋千金藤立定(SPD)对血清催乳素(PRL)水平的影响,研究SPD的药理作用。方法:成熟♀鼠ip多巴胺受体激动剂、拮抗剂或SPD后断头取血,然后用放射免疫法测定血清中的催乳素水平。结果:SPD引起血清PRL水平迅速而显著的增加,效应持续约1h,具有剂量依赖性。SPD的半数有效剂量为3.7mg·kg~(-1)(95％可信限为2.6—4.3mg·kg~(-1))。剂量为20mg·kg~(-1)时产 生最大效应,使血清PRL水平达到448±64μg·L~(-1),0.2mg·kg~(-1)则无效。对于多巴胺受体激动剂培高利特(pergolide)引起的PRL水平低下,SPD5mg·kg~(-1)有部分对抗作用,10mg·kg~(-1)能够完全对抗。结论:SPD是D_2多巴胺受体拮抗剂。     

慢性给予左旋千金藤立定对纹状体多巴胺D_1和D_2受体密度和更新率的影响

慢性给予左旋千金藤立定对纹状体多巴胺Ｄ１和Ｄ２受体密度和更新率的影响１邹灵龙，蔡舒天，金国章２（中国科学院上海药物研究所，上海２０００３１，中国关键词左旋千金藤立定；纹状体；ＳＣＨ２３３９０；放射配位体测定；多巴胺Ｄ１受体；多巴胺Ｄ２受体目的：观察...     

北五味子提取液对小鼠耐缺氧及抗疲劳能力的影响

目的研究北五味子提取液（SCE）对小鼠耐缺氧和抗疲劳能力的影响。方法健康昆明种小鼠随机分为空白对照组和SCE低、中、高剂量组,连续灌胃7d。观察小鼠常压耐缺氧存活时间和负重游泳时间。结果SCE能显著增加小鼠常压缺氧存活时间和负重游泳时间。结论SCE能够明显提高小鼠耐缺氧和抗疲劳的能力。     

Effects of dopamine antagonists on methamphetamine-induced dopamine release in high and low alcohol preference rats

The authors have previously shown that high alcohol preference rats (HAP) have a significantly higher sensitivity than low alcohol preference rats (LAP) for methamphetamine (MAP). In this study, changes in dopamine and serotonin release induced by MAP (1?mg/kg, intraperitoneally) after pre-treatment with D1 and D2 receptor antagonists were examined in the striatum of rats with different alcohol preferences to elucidate differences in receptor levels between the two rat strains. D1 receptor antagonist SCH23390 or D2 receptor antagonist haloperidol were administrated intracerebroventricularly 10?min before MAP stimulation. This study investigated the effect of methamphetamine-induced dopamine and serotonin release in striatum using microdialysis of freely moving rats coupled to ECD-HPLC. With haloperidol treatment both strains of rats showed a significantly greater maximum increase on MAP-induced dopamine release compared with respective control rats. However, after SCH23390 treatment only HAP rats showed a significantly greater increase in dopamine release compared with controls. SCH23390 blocks mainly D1 receptors only in the post-synaptic membrane, whereas haloperidol blocks D2 receptors in both the pre-synaptic and post-synaptic membranes. The MAP-induced increase in dopamine release following haloperidol pre-treatment was greater than SCH23390 pre-treatment in both strains. This result indicates that D2 receptors (autoreceptors) in the pre-synaptic membrane were blocked, leading to the elimination of the feedback function that regulates dopamine release. These data suggested that alcohol preference is associated with the action of MAP, and the dopaminergic mechanism, specifically the D1 system in the striatum, might have a different pathway dependent on alcohol preference.     

The effects of selective dopamine receptor agonists and antagonists on body temperature in rats

Body temperature was measured at repeated time intervals following the administration of various dopamine agonists and antagonists. The D-1 and D-2 receptor agonist, apomorphine, produced dose-dependent hypothermia. This effect was inhibited by the D-2 receptor antagonist, spiroperidol. Stimulation of D-2 receptor by LY171555 produced dose-dependent hypothermia, which was attenuated by pretreatment with spiroperidol and not altered by the D-1 receptor antagonist SCH23390. The D-1 receptor agonist, SK&F38393 had no effect on body temperature. SCH23390 administered alone produced initial hyperthermia and subsequent hypothermia. When administered with apomorphine, SCH23390 both attenuated and potentiated the hypothermic response, depending on the dose and time of administration of each drug. The results suggest that dopamine receptor agonists induce hypothermia by stimulation of the D-2 receptor subtype.     

The effect of dopamine receptor agonist treatment on haloperidol-induced supersensitivity in mice

Mice were pretreated with haloperidol (HP) (3-4 mg/kg/day in drinking water) or vehicle for 21 days. On the 25th day, HP-pretreated mice were supersensitive to the locomotor stimulant effects of apomorphine (after acute premedication with reserpine and alpha-methyl-p-tyrosine). This behavioural supersensitivity was accompanied by a 25-39% increase in the number of [3H]-spiperone binding sites in the striata of HP-pretreated mice. Short-term repeated administration of the dopamine (DA) agonist drugs d-amphetamine and L-DOPA during the HP withdrawal phase (days 22, 23 and 24) had no effect on either measure of DA receptor supersensitivity. In contrast, the administration of apomorphine on days 22, 23 and 24 enhanced the HP-induced behavioural supersensitivity but decreased the HP-induced elevation of the number of [3H]-spiperone binding sites. Apomorphine treatment alone did not alter either measure. The results do not support the hypothesis that supersensitive DA receptors can be down-regulated by short-term treatment with DA agonist drugs and, moreover, indicate that important discrepancies may exist between behavioural and biochemical measures of DA receptor supersensitivity.     

Effects of dopamine receptor antagonists on the acquisition of ethanol-induced conditioned place preference in mice

Rationale

Studies support differential roles of dopamine receptor subfamilies in the rewarding and reinforcing properties of drugs of abuse, including ethanol. However, the roles these receptor subfamilies play in ethanol reward are not fully delineated.

Objective

To examine the roles of dopamine receptor subfamilies in the acquisition of ethanol-induced conditioned place preference (CPP), we pretreated animals systemically with antagonist drugs selective for dopamine D1-like (SCH-23390) and D2-like (raclopride) receptors prior to ethanol conditioning trials.

Methods

Effects of raclopride (0–1.2 mg/kg) and SCH-23390 (0–0.3 mg/kg) on the acquisition of ethanol-induced CPP were examined in DBA/2J mice (experiments 1 and 2). Based on significant effects of SCH-23390, we then determined if SCH-23390 (0.3 mg/kg) produced a place preference on its own (experiment 3). To evaluate whether SCH-23390 impaired learning, we used a conditioned place aversion (CPA) paradigm and pretreated animals with SCH-23390 (0–0.3 mg/kg) before conditioning sessions with LiCl (experiment 4).

Results

Whereas raclopride (0–1.2 mg/kg) did not affect acquisition, SCH-23390 (0.1–0.3 mg/kg) impaired the development of ethanol-induced CPP. SCH-23390 (0.3 mg/kg) did not produce place preference when tested alone and SCH-23390 (0.1–0.3 mg/kg) did not perturb the acquisition of LiCl-induced CPA.

Conclusions

Our results support a role for dopamine D1-like but not D2-like receptors in ethanol’s unconditioned rewarding effect as indexed by CPP. Blockade of D1-like receptors did not affect aversive learning in this procedure.     

Effects of dopamine receptor antagonists on sucrose consumption and preference

Effects of the dopamine D2 receptor antagonist sulpiride and the D1 antagonist SCH-23390 were examined, in rats, in two-bottle preference tests (sucrose versus water) and in single-bottle tests, at different sucrose concentrations. Both drugs decreased sucrose intake in single bottle tests, at low sucrose concentrations, but had no effect at high concentrations; reducing drive level had exactly the opposite pattern of effects. In two-bottle tests, both drugs reduced preference for the weakest sucrose concetration (0.7%) but increased preference for the strongest concentration (34%). The effects of antagonizing either subtype of DA receptor appear to be similar to those of reducing the concentration of sucrose.     

The effects of dopamine D-1 and D-2 receptor agonists on body temperature in male mice

The effect of dopamine D-1 and D-2 receptor stimulation on body temperature has been investigated in male mice. The selective D-2 receptor agonists, quinpirole and LY 163502, and the mixed D-1/D-2 agonist, apomorphine, induced a dose-dependent hypothermia, whereas the selective D-1 receptor agonists, SK&F 81297, SK&F 38393 and SK&F 75670, induced hyperthermia. The hyperthermic responses of these agents were of a similar magnitude although the relative efficacies determined in vitro with the adenylate cyclase assay were different. The peripherally acting D-1 agonist, fenoldopam, did not influence body temperature, indicating that the hyperthermia is mediated, centrally. Studies with combinations of quinpirole and SK&F 38393 showed that the effect of one of the substances could be counteracted by the other. Furthermore, antagonist studies showed that the hypothermia induced by quinpirole could be inhibited by the D-2-selective antagonist, YM 09151-2, and by the mixed D-1/D-2 antagonist, cis(Z)-flupentixol, but not by the D-1-selective antagonist, SCH 23390. Similar results were found for apomorphine-induced hypothermia. SK&F 38393-induced hyperthermia could be antagonized by all three antagonists. These results suggest that the two receptor subtypes act differentially on body temperature, and that they influence a common out-put system, but in opposite directions. These findings are opposite to those of behavioural studies, where a synergistic function of D-1 and D-2 receptors has been demonstrated in the regulation of motor function.     

Effects of dopamine receptor antagonists on ongoing maternal behavior in rats

The effects of different peripheral doses of four dopamine (DA) receptor antagonists on general activity and maternal behavior were examined in lactating female rats. Administration of the classic D1-like and D2-like DA receptor blocker haloperidol (0.1 and 0.05 mg/kg) disrupted pup retrieval and nest-building behaviors and reduced motor activity. Pimozide (0.5 and 0.2 mg/kg), which has more affinity for DA D2-like receptors, mildly disrupted pup retrieval while showing no significant influence on open-field behaviors. The putative DA D(4) receptor blocker, clozapine (1.5 and 1.0 mg/kg) reduced motor activity significantly, while only 1.0 mg/kg dose significantly decreased percent of rats displaying nest building. The DA D1-like receptor blocker SKF-83566 (0.2 and 0.1 mg/kg) significantly reduced pup retrieval, nest building and motor activity. These results suggest a role for DA receptors in ongoing maternal behavior that correlates directly with general activity.     

淫羊藿总黄酮对小鼠心肌缺氧的保护作用

目的：观察淫羊藿总黄酮对小鼠急性心肌缺氧的保护作用。方法：常压缺氧条件下分别观察小鼠平均存活时间和心肌耗氧量；采用夹闲气管法观察小鼠平均心电消失时间。结果：淫羊藿总黄酮高、低剂量组均能延长小鼠平均存活时间，降低心肌耗氧量。结论：淫羊藿总黄酮能明显降低小鼠心肌氧耗，保护缺氧心肌，延长小鼠存活时间。     

Effects of dopamine receptor antagonists on gastrin and vomiting responses to apomorphine

Summary Apomorphine (0.05 mg/kg intravenously) was given to conscious dogs, and gastrin levels were measured in peripheral venous blood with a radioimmunoassay. Apomorphine induced an increase of gastrin levels which peaked at 5 min. The peripheral dopamine D-2/DA₂ receptor antagonist domperidone (0.2 mg/kg), but not halopemide (0.1–1 mg/kg) nor the D-1 /DA₁ receptor antagonist SCH 23390 (0.1 mg/kg), blocked the gastrin response to apomorphine. Both domperidone and halopemide, but not SCH 23 390, blocked the Apomorphine-induced vomiting. These results suggest that apomorphine increases gastrin levels by an action at D-2/DA₂ receptors, which are situated outside the blood brain barrier and differ from the receptor inducing the vomiting. Send offprint requests to M. Goiny at the above address     

Effects of chlorpromazine,thioridazine and haloperidol on adrenergic transmitter mechanisms in man

Summary Two methods have recently been described for determining the effect of psychotropic drugs on noradrenergic nerves. Membrane pump blockade can be quantified by inhibition of uptake of³H-noradrenaline (NA) by rat irides incubated in drug-containing plasma. Tyramine, an indirectly acting sympathomimetic, produces a temporary rise in blood pressure after intravenous injection and may also be used to quantify the effect of drugs on adrenergic transmitter mechanisms in man. Patients taking the neuroleptics, chlorpromazine, thioridazine and haloperidol have been studied. Using these two methods, haloperidol had no effect on noradrenergic transmitter mechanisms. Thioridazine also had no effect on the NA membrane pump but produced slight receptor blockade. Chlorpromazine had an inhibitory effect on the NA uptake mechanism of the rat iris, both in model experiments and in plasma from patients. The blockade was less than that produced by nortriptyline. The results of the tyramine test were similar to those obtained after nortriptyline. The discrepancy is probably due to blockade of the NA receptor by chlorpromazine.The neuroleptic drugs appear to have in common the ability to produce blockade of central dopamine receptors and this has been proposed as the explanation of their antipsychotic effect. There is probably no simple relationship between the effects of these drugs on NA transmitter mechanisms and their antipsychotic effects. The widespread effects of chlorpromazine on monoamine transmitter mechanisms might, however, account for its continued popularity, often as the drug of choice, in treating psychoses, despite the introduction of many other neuroleptics.