Reversal of stress-induced anhedonia by the dopamine receptor agonist,pramipexole

Chronic exposure to mild unpredictable stress has previously been found to depress the consumption of a palatable (1%) sucrose solution, and to attenuate food-induced place preference conditioning. In this study the effects of pramipexole (SND-919), a dopamine D₂ agonist, were studied during 7–9 weeks of chronic treatment. Pramipexole (1.0 mg/kg per day) reversed the suppression of sucrose intake in stressed animals, increasing sucrose intakes above the levels seen in untreated nonstressed controls. Pramipexole also increased sucrose intake in nonstressed animals; these effects were accompanied by increases in water intake and tended to correlate with weight loss. Drug-treated stressed animals also lost weight, but in this case water intake was unaffected. A second group of animals received a higher dose of pramipexole (2.0 mg/kg per day). The effects of the two doses were very similar. After three weeks of treatment, these animals were switched to a lower dose of pramipexole (0.1 mg/kg per day). Increases in sucrose intake were maintained over three weeks of treatment at the lower dose, with significant recovery of body weight. Two further groups received the same doses of pramipexole (1.0 mg/kg for 6 weeks or 2.0 mg/kg for 3 weeks followed by 0.1 mg/kg thereafter), but received intermittent (twice-weekly) drug treatment. Intermittent pramipexole treatments also tended to increase sucrose intakes, but the results were less consistent from week to week. Following 6–8 weeks of pramipexole treatment, food-induced place preference conditioning was studied in all animals. Untreated stressed animals showed no evidence of place conditioning. Normal conditioning was seen in both groups of stressed animals treated daily with pramipexole (at 1.0 and 0.1 mg/kg) and in the group treated twice weekly at the higher dose (1.0 mg/kg); intermittent treatment at the lower dose (0.1 mg/kg) was ineffective. The results indicate that pramipexole exerts rapid anti-anhedonic effects in the chronic mild stress model. This conclusion is complicated, but not undermined, by drug-induced weight loss and by the presence of significant drug effects in nonstressed control animals.     

多巴丝肼联合盐酸普拉克索治疗帕金森病对运动功能的影响研究

目的探究帕金森病患者应用多巴丝肼联合盐酸普拉克索治疗对运动功能的影响。方法100例帕金森病患者,随机分为对照组与观察组,各50例。对照组患者给予多巴丝肼治疗,观察组患者给予多巴丝肼联合盐酸普拉克索治疗。比较两组患者的运动功能和不良反应发生情况。结果观察组患者左手运动、右手运动、起立、转弯、10 m折返运动时间分别为(94.06±5.23)、(98.64±8.03)、(3.03±0.25)、(4.44±0.84)、(13.48±0.72)min,均长于对照组的(86.13±4.02)、(88.65±5.46)、(2.23±0.12)、(2.98±0.48)、(13.94±0.62)min,差异有统计学意义(P<0.05)。治疗前及治疗4周,两组帕金森病综合评分量表(UPDRS)评分比较差异无统计学意义(P>0.05);观察组治疗8、12周UPDRS评分均低于对照组,差异有统计学意义(P<0.05)。两组不良反应发生率比较差异无统计学意义(χ2=3.053,P>0.05)。结论应用多巴丝肼联合盐酸普拉克索治疗帕金森病患者效果显著,可有效改善运动功能,临床价值高。     

多巴丝肼联合普拉克索治疗帕金森综合征的效果观察

目的:观察多巴丝肼联合普拉克索治疗帕金森综合征的临床效果。方法:选取收治的40例帕金森综合征患者为研究对象,采用随机数字表法分为研究组和对照组,每组20例。对照组予多巴丝肼治疗,研究组在对照组基础上联合普拉克索治疗,比较两组治疗前后帕金森病评定量表(UPDRS)评分,临床疗效及治疗后运动功能。结果:治疗后,两组UPDRS评分均低于治疗前,且研究组低于对照组,差异均有统计学意义(P<0.05);研究组治疗总有效率为95.00%,高于对照组的60.00%,差异有统计学意义(P<0.05);研究组左手及右手1 min限时运动次数均多于对照组,差异有统计学意义(P<0.05);研究组10 m步行折返起立耗时及转弯耗时均短于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:多巴丝肼联合普拉克索治疗帕金森综合征,可有效改善患者的临床症状,改善预后。     

2011-2013年江苏省江原医院门诊普拉克索使用分析

目的：了解江苏省原子医学研究所附属江苏省江原医院（以下简称“我院”）门诊普拉克索使用情况,为临床合理用药提供参考。方法：抽取我院2011—2013年诊断为帕金森病（ PD）的所有门诊处方共计7688张,从中随机抽取1200张,收集患者的性别、年龄、用药情况等信息资料,对不同年龄段患者用药情况进行统计分析。结果：普拉克索在70岁以下患者中用量较大,随着年龄的增长,使用普拉克索的处方数比例逐渐下降,＜50岁、50～＜60岁、60～＜65岁、65～＜70岁年龄段使用普拉克索比例分别为80.70％、65.28％、64.81％、55.03％;而联合使用复方左旋多巴的处方数比例逐渐增加。普拉克索销售金额和用药频度（DDDs）增长很快,限定日费用（ DDC）较高。结论：我院普拉克索的使用比较合理,符合PD治疗指南,但由于普拉克索价格较贵,患者经济负担较重,因此在药物选择上需要根据患者病情的特点、年龄、职业、经济状况等因素综合考虑,从中选择比较合适药物,以便于提高患者的生活质量。     

Sleep episodes and daytime somnolence as result of individual susceptibility to different dopaminergic drugs in a PD patient: a polysomnographic study

The association between excessive daytime somnolence (EDS) and idiopathic Parkinson's disease (PD) is often reported but still debated. The possible role of antiparkinsonian therapy or primarily of PD on excessive diurnal sleepiness is controversial.We describe the case of a 61-year-old patient affected by PD who experienced sleep episodes (SE) occurring during pramipexole plus l-Dopa therapy. Polysomnographic sleep studies and subjective evaluations of daytime sleepiness (Epworth Sleepiness Scale) were carried out under administration of pramipexole plus l-Dopa, l-Dopa monotherapy and cabergoline plus l-Dopa. The polysomnography revealed two sleep events during pramipexole plus l-Dopa. Moreover, the polysomnographic data showed an increase of both diurnal and nocturnal sleep under pramipexole plus l-Dopa compared with cabergoline plus l-Dopa and l-Dopa as monotherapy. In addition, while Epworth Sleepiness Scale (ESS) Score showed a mild sleepiness under pramipexole (ESS score=11), ESS scores were normal under both l-Dopa and cabergoline plus l-Dopa. Sleep episodes also disappeared under both l-Dopa and cabergoline plus l-Dopa (2- and 12-month follow-up). We hypothesize that an individual susceptibility to specific antiparkinsonian drug may play a significant role in the genesis of sleepiness in our PD patient.     

The activity of pramipexole in the mouse forced swim test is mediated by D<Subscript>2</Subscript> rather than D<Subscript>3</Subscript> receptors

Rationale Recent studies have reported antidepressant-like activities of the dopamine D₂/D₃ agonist pramipexole in the chronic mild stress model and in the forced swim test, suggesting that D₃ receptor agonists may represent a new class of antidepressant drugs. However, the relative contribution of D₂ or D₃ receptors to the activity of pramipexole in these models is unclear.Objectives The aim of the current studies was to explore the role of dopamine D₂ and D₃ receptors in the activity of pramipexole in the mouse forced swim test.Methods The effect of pramipexole (0.1–3.2 mg/kg) in the mouse forced swim test was examined both in conjunction with D₂ and D₃ receptor antagonists (haloperidol (0.1–1 mg/kg) and LU-201640 (A-437203, 5.6–17.8 mg/kg), as well as in D₃ receptor knockout mice obtained on two different background strains (C57BL/6J and B6129SF2/J). Locomotor activity was also assessed following pramipexole administration.Results Pramipexole produced dose-dependent reductions in immobility in the forced swim test at doses that did not produce generalized increases in locomotor activity. LU-201640, the D₃ selective antagonist, failed to block the antidepressant-like effects of pramipexole. In contrast, the efficacy of pramipexole in the forced swim test was completely blocked by the D₂ antagonist, haloperidol. No baseline differences were observed between knockout and wild-type mice from either background strain in locomotor activity or in the forced swim test. Furthermore, in both background strains, pramipexole showed similar efficacy in the forced swim test for both wild-type and knockout mice.Conclusions Taken together, these studies suggest that the D₂ receptor rather than the D₃ receptor is important for the antidepressant-like activity observed for pramipexole in the mouse forced swim test.Portions of this work were presented at the 36th Winter Conference on Brain Research, Snowbird, UT, January 26–31, 2003.     

添加普拉克索治疗对帕金森病患者UPDRS评分及非运动症状的影响分析

目的探讨添加普拉克索治疗对帕金森病患者的统一帕金森病量表(UPDRS)评分及非运动症状的影响,同时观察治疗安全性。方法按照随机数字法分为对照组(71例)和观察组(74例),对照组患者给予复方左旋多巴治疗,观察组患者在使用复方左旋多巴的基础上添加普拉克索治疗,比较两组患者治疗前后UPDRSⅡ、Ⅲ评分及汉密尔顿抑郁量表(HAMD)及简易精神状态检查(MMSE)量表评分,比较两组患者的睡眠障碍,感觉异常,尿频尿急,便秘和流涎等非运动症状改善情况,及治疗后各种不良反应发生率。结果治疗后两组患者UPDRSⅡ、Ⅲ评分明显低于治疗前,且观察组显著优于对照组(P0.05)。治疗后,观察组与对照组相比HAMD评分有明显降低(P0.05),而MMSE评分无明显差异(P0.05)。治疗后,两组患者睡眠障碍、感觉异常和尿频尿急的发生率有明显下降、且观察组低于对照组(P0.05),而便秘和流涎的发生率无明显变化(P0.05)。观察组患者的不良反应发生率为(9.46%),对照组患者的不良反应发生率为(16.90%),两组患者差异明显(P0.05)。结论添加普拉克索治疗帕金森病的疗效明显,能提高PD患者的运动功能和日常生活能力,缓解忧郁、焦虑等不良情绪的发生,同时能有效改善患者的部分非部分运动症状,不良反应发生率较低。     

普拉克索治疗帕金森病有效性和安全性的meta分析

目的通过对普拉克索治疗帕金森病(PD)的临床随机对照研究进行Meta分析,探讨普拉克索的药效和安全性,为临床安全合理使用该药提供依据。方法计算机检索Ovid Medline(1966年~2009年3月),图书馆临床试验和专业资料库,Cochrane图书馆临床对照试验资料库(ACP Journal C1ub;Cochrane Central Register ofControlled Trials CENTRAL,2008年),中国生物医学文献数据库(1990~2008年),同时检索相关文献的参考文献。应用Cochrane协作网提供的Rev Man4.28软件系统评价,对普拉克索治疗PD的随机对照试验进行Meta分析。结果共纳入6个随机对照试验,包括普拉克索组898例患者,安慰剂对照组813例患者。Meta分析结果显示:(1)帕金森病评定量表(UPDRS)第Ⅱ部分评分相对基线的变化取加权均数差进行meta分析。普拉克索组和安慰剂组之间差异(WMD=-2.35,95%CI[-2.92,-1.79],P<0.01),差异有统计学意义。UPDRSⅢ评分相对基线的变化取加权均数差进行meta分析。普拉克索组和对照组之间...     

普拉克索治疗原发性不宁腿综合征的临床研究

目的观察普拉克索治疗原发性不宁腿综合征(RLS)的效果和安全性。方法选择自2009年11月至2011年11月在我院就诊的28例原发性RLS患者,给予普拉克索0.125～0.75mg,持续治疗12周。利用国际RLS研究小组的RIS严重程度量表(IRIS)对患者治疗前后的IRLS症状严重程度进行评估,并对结果进行统计学分析。结果治疗后患者的IRIS评分较治疗前明显降低,比较差异有统计学意义(P<0.05)。结论普拉克索治疗原发性RLS是安全有效的。目的观察普拉克索治疗原发性不宁腿综合征(RLS)的效果和安全性。方法选择自2009年11月至2011年11月在我院就诊的28例原发性RLS患者,给予普拉克索0.125～0.75mg,持续治疗12周。利用国际RLS研究小组的RIS严重程度量表(IRIS)对患者治疗前后的IRLS症状严重程度进行评估,并对结果进行统计学分析。结果治疗后患者的IRIS评分较治疗前明显降低,比较差异有统计学意义(P<0.05)。结论普拉克索治疗原发性RLS是安全有效的。     

Effects of pramipexole on the duration of immobility during the forced swim test in normal and ACTH-treated rats

The dopamine D2/D3 receptor agonist pramipexole has clinically been proven to improve depression or treatment-resistant depression. However, the involvement of the dopamine receptor system on the effect of pramipexole on depression remains unclear. We examined the influence of pramipexole on the duration of immobility during the forced swim test in normal and adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of dopamine receptors in this effect. Additionally, the mechanism by which pramipexole acts in this model was explored specifically in relation to the site of action through the use of microinjections into the intramedial prefrontal cortex and nucleus accumbens. Pramipexole (0.3–1 mg/kg) significantly decreased the duration of immobility in normal and ACTH-treated rats. This effect was blocked by L-741,626, a D2 receptor antagonist, and nafadotride, a D3 receptor antagonist, in normal rats. Furthermore, infusions of pramipexole into the intranucleus accumbens, but not the medial prefrontal cortex, decreased the immobility of normal and ACTH-treated rats during the forced swim test. Taken together, the results of these experiments suggested that pramipexole, administered into the intranucleus accumbens rather than the medial prefrontal cortex, exerted an antidepressant-like effect on ACTH-treated rats via the dopaminergic system. The immobility-decreasing effect of pramipexole may be mediated by dopamine D2 and D3 receptors.