吗啡对吗啡依赖大鼠腹侧苍白球神经元放电的影响

目的 :研究吗啡对吗啡依赖大鼠腹侧苍白球的电生理影响 ,探讨其在成瘾机制中的作用。方法 :通过单细胞细胞外记录吗啡依赖大鼠腹侧苍白球的电信号 ,观察吗啡对放电的影响。结果 :吗啡依赖大鼠腹侧苍白球神经元放电频率给药前为 3 76Hz±s 1 18Hz,注射吗啡后为 13 2 2Hz±s 2 37Hz;并且纳洛酮可以逆转这种兴奋效应。结论 :吗啡显著兴奋吗啡依赖大鼠腹侧苍白球神经元 ,腹侧苍白球在药物强化过程中起着重要作用。     

γ-氨基丁酸及拮抗剂对大鼠黑质玫密部神经元活动的影响

目的：研究伸γ-基丁酸（γ-Aminobutyrie Acid，GABA）和GABAA受体阻断剂荷包牡丹碱（Bicuculine，Bic）对大鼠黑质致密部（pars compacta of substantia nigra，SNc）神经元自发放电活动的影响。方法：采用微电泳及细胞外记录方法观察GABA和Bic对SNc神经元自发放电活动的影响。结果：GABA使42个受试神经元自发放电活动几乎完全停止。在30个受试神经元中，Bic使22个神经元放电频率加快，6个神经元无作用，2个神经元受到抑制。在35个受试神经元中，微电泳GABA期间给予GABAA受体阻断剂Bic，其可使91．43％神经元放电频率加快。结论：GABA能投射对SNc神经元有抑制作用，GABAA受体阻断剂Bic能拮抗GABA的抑制作用。     

SNP、GLU及GABA对纹状体神经元活动的影响

目的　探讨一氧化氮(NO)在纹状体(STR)信息传递中的作用,对帕金森综合征(PD)的发病机制有更深入的了解,对PD的临床诊断及治疗有更深远的帮助。方法　本实验采用多管玻璃微电极微电泳方法观察了微电泳硝普钠(SNP)、谷氨酸(GLU)及γ- 氨基丁酸(GABA)对大鼠STR神经元自发放电的影响。同时观察了NO对GLU及GABA神经传递的影响。结果　实验观察到微电泳SNP可使77%(51 /66)受试神经元放电频率加快,其兴奋作用可被单硝基L -精氨酸甲酯(L NAME)所拮抗。在微电泳GLU或GABA过程中,给予SNP可增强GLU的兴奋作用,拮抗GABA的抑制作用。给予NOS抑制剂L- NAME可拮抗GLU的兴奋作用。结论　实验结果表明NO、GABA、GLU等神经递质活动在STR的同一神经元有会聚作用,NO、GLU对STR神经元有兴奋作用,而GABA对STR神经元有紧张性抑制作用。     

γ-氨基丁酸及拮抗剂对大鼠黑质致密部神经元活动的影响

目的:研究γ-氨基丁酸(γ-Aminobutyric Acid,GABA)和GABAA受体阻断剂荷包牡丹碱(Bicuculine,Bic)对大鼠黑质致密部(pars compacta of substantia nigra,SNc)神经元自发放电活动的影响。方法:采用微电泳及细胞外记录方法观察GABA和Bic对SNc神经元自发放电活动的影响。结果:GABA使42个受试神经元自发放电活动几乎完全停止。在30个受试神经元中,Bic使22个神经元放电频率加快,6个神经元无作用,2个神经元受到抑制。在35个受试神经元中,微电泳GABA期间给予GABAA受体阻断剂Bic,其可使91.43%神经元放电频率加快。结论:GABA能投射对SNc神经元有抑制作用,GABAA受体阻断剂Bic能拮抗GABA的抑制作用。     

不同频率电刺激VTA对吗啡成瘾大鼠ACbSh的放电活动的影响

目的:观察电刺激大鼠腹侧被盖区(VTA)对吗啡成瘾大鼠伏隔核壳部(ACbSh)神经元的影响,为应用脑深部电刺激技术治疗阿片类药物成瘾提供实验依据。方法:采用单管玻璃微电极细胞外记录法,观察不同频率电刺激VTA对吗啡成瘾大鼠ACbSh神经元放电的影响。结果:低频(50Hz)电刺激VTA,吗啡组ACbSh神经元主要表现为无反应(47.83%);高频(135Hz)电刺激VTA,吗啡组多数ACbSh神经元表现为抑制性作用(50.00%)。结论:高频电刺激VTA有可能作为新方法用于治疗阿片类药物成瘾。     

神经肽优洛可定对丘脑底核神经元自发放电影响与CRF-2R关系研究

目的研究神经内分泌生物活性肽优洛可定(urocortin,UCN)对丘脑底核(subthalamic nucleus,STN)神经元放电及STN中多巴胺(dopamine,DA)能、谷氨酸(glutamic acid,GLU)能神经传递的影响,研究UCN在STN中是否与GLU及DA存在汇聚作用,探讨UCN在帕金森疾病(Parkinson’s disease,PD)发生中可能发挥的作用。方法取40只SD大鼠,采用神经电生理实验方法中的微电泳技术,在微电泳UCN过程中,观察STN神经元放电的波形及频率变化,同时,微电泳Astressin(AST)及蛋白激酶A(protein kinase A,PKA)抑制剂,观察促皮质素释放因子2型受体(corticotropin releasing factor 2 receptor,CRF-2R)是否参与UCN对STN神经元放电的影响。另外,在微电泳DA和GLU过程中,给予UCN及AST,观察STN神经元放电的变化,明确是否存在DA能及GLU能与UCN的交汇作用。结果微电泳UCN过程中,82%(27/33)STN神经元频率减慢。STN平均放电频率由(3.65±0.27)Hz减少到(2.05±0.33)Hz,微电泳UCN前、后STN放电频率明显降低(P<0.01)。另外,UCN抑制作用可被AST明显拮抗(P<0.01),UCN抑制作用也可被PKA阻断剂部分阻断。在微电泳抑制性神经递质DA和兴奋性GLU过程中,UCN能进一步协同DA的抑制效应,并明显拮抗GLU的兴奋作用(P<0.01)。结论 UCN与DA能及GLU能在STN神经元中存在汇聚作用,UCN可能是通过与CRF-2R结合,进而通过PKA信号通路,影响DA能、GLU能神经递质活动,抑制STN神经元放电。     

微电泳urocortinⅡ对大鼠纹状体神经元自发放电及DA、ACH能神经传递影响

帕金森病(Parkinsoncs disease, PD) 是常见的中枢神经系统退行性病变,其主要病理特征为黑质-纹状体多巴胺(dopamine, DA) 能神经元变性缺失,乙酰胆碱(acetylcholine, ACH)能过度兴奋[1].其常见的发病机制包括:兴奋毒性、细胞凋亡及氧化应激学说[1-2].有研究表明,新型神经肽(urocortin, UCN)具有神经元保护作用,可用于PD、阿尔采末病等疾病的治疗[3-4].UCN是一种40个氨基酸小分子神经肽,由下丘脑分泌后刺激垂体前叶细胞释放促肾上腺皮质激素和β-内啡肽.目前研究认为UCN 可能具有神经系统保护功能[5-6],然而,UCN对基底神经节神经元放电的影响及对其他神经递质间的相互协调作用,未见报道.     

深部电刺激诱导6-OHDA损伤鼠纹状体神经介质和KATP通道亚单位mRNA的改变

目的探索深部电刺激（deep brain stimulation,DBS）对6-OHDA损伤鼠纹状体神经介质的影响及其对纹状体KATP通道亚单位mRNA的改变。方法采用立体定向的方法将电极置于6-OHDA损伤鼠右侧脑丘脑底核（subthalamic nucleus,STN）进行深部电刺激,分离出大鼠脑纹状体后用高效液相法测定DA、Glu、GABA的浓度,并用RT-PCR检测KATP通道亚单位mRNA的改变。结果DBS显著增加6-OHDA损伤鼠纹状体中DA、Glu、GABA的浓度,同时RT-PCR检测也发现,DBS增强Kir6.1,Kir6.2mRNA的表达。结论DBS可能通过增强Kir6.1,Kir6.2 mRNA的表达而影响大鼠脑纹状体中DA、Glu、GABA的浓度。     

电刺激小脑顶核对急性脑缺血中细胞间黏附作用的影响

目的探讨电刺激小脑顶核对急性脑缺血中细胞间黏附作用的影响。方法成年雄性Wistar大鼠32只,随机分为4组,即正常对照组、伪手术组、脑缺血-再灌注损伤组（脑缺血组）、脑缺血-再灌注损伤组加电刺激小脑顶核（fastigial nucleus stimulation,FNs）组,每组为8只大鼠。分离培养大鼠脑毛细血管内皮细胞（cerebral capillary vessel endothelialcell,CCEC）和多形核白细胞（polymorphism nuclear leucoeyte,PMN）,利用微管吸吮技术,观察各组CCEC和PMN间黏附力特性的变化。结果脑缺血-再灌注后各时间点CCEC和PMN的黏附力和黏附应力均明显高于正常对照组和伪手术组（P〈0．01）;电刺激小脑顶核后,CCEC和PMN的黏附力及黏附应力均明显下降（P〈0．05）。结论脑缺血-再灌注损伤后,电刺激小脑顶核可抑制CCEC和PMN的黏附,减轻脑损伤。     

Neuronal Responses in the Globus Pallidus during Subthalamic Nucleus Electrical Stimulation in Normal and Parkinson's Disease Model Rats

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been widely used as a treatment for the movement disturbances caused by Parkinson''s disease (PD). Despite successful application of DBS, its mechanism of therapeutic effect is not clearly understood. Because PD results from the degeneration of dopamine neurons that affect the basal ganglia (BG) network, investigation of neuronal responses of BG neurons during STN DBS can provide informative insights for the understanding of the mechanism of therapeutic effect. However, it is difficult to observe neuronal activity during DBS because of large stimulation artifacts. Here, we report the observation of neuronal activities of the globus pallidus (GP) in normal and PD model rats during electrical stimulation of the STN. A custom artifact removal technique was devised to enable monitoring of neural activity during stimulation. We investigated how GP neurons responded to STN stimulation at various stimulation frequencies (10, 50, 90 and 130 Hz). It was observed that activities of GP neurons were modulated by stimulation frequency of the STN and significantly inhibited by high frequency stimulation above 50 Hz. These findings suggest that GP neuronal activity is effectively modulated by STN stimulation and strongly dependent on the frequency of stimulation.     

Long-Term Effects of Nucleus Accumbens Deep Brain Stimulation in Treatment-Resistant Depression: Evidence for Sustained Efficacy

Deep brain stimulation (DBS) to the nucleus accumbens (NAcc-DBS) was associated withantidepressant, anxiolytic, and procognitive effects in a small sample of patientssuffering from treatment-resistant depression (TRD), followed over 1 year. Results oflong-term follow-up of up to 4 years of NAcc-DBS are described in a group of 11 patients.Clinical effects, quality of life (QoL), cognition, and safety are reported. Elevenpatients were stimulated with DBS bilateral to the NAcc. Main outcome measures wereclinical effect (Hamilton Depression Rating Scale, Montgomery-Asperg Rating Scale ofDepression, and Hamilton Anxiety Scale) QoL (SF-36), cognition and safety at baseline, 12months (n=11), 24 months (n=10), and last follow-up(maximum 4 years, n=5). Analyses were performed in an intent-to-treatmethod with last observation carried forward, thus 11 patients contributed to each pointin time. In all, 5 of 11 patients (45%) were classified as responders after 12months and remained sustained responders without worsening of symptoms until lastfollow-up after 4 years. Both ratings of depression and anxiety were significantly reducedin the sample as a whole from first month of NAcc-DBS on. All patients improved in QoLmeasures. One non-responder committed suicide. No severe adverse events related toparameter change were reported. First-time, preliminary long-term data on NAcc-DBS havedemonstrated a stable antidepressant and anxiolytic effect and an amelioration of QoL inthis small sample of patients suffering from TRD. None of the responders of first yearrelapsed during the observational period (up to 4 years).     

GABAA receptor in the Pedunculopontine tegmental (PPT) nucleus: Effects on cardiovascular system

Background

The pedunculopontine tegmental (PPT) nucleus is a heterogeneous nucleus with several functions including cardiovascular regulation. The presence of GABA_A receptor has been shown in the PPT. Therefore, the cardiovascular effects of this receptor were examined.

c-Fos Expression in the Nucleus of the Solitary Tract in Response to Salt Stimulation in Rats

Salt signals in tongue are relayed to the nucleus of the solitary tract (NST). This signaling is very important to determine whether to swallow salt-related nutrition or not and suggests some implications in discrimination of salt concentration. Salt concentration-dependent electrical responses in the chorda tympani and the NST were well reported. But salt concentration-dependency and spatial distribution of c-Fos in the NST were not well established. In the present study, NaCl signaling in the NST was studied in urethane-anesthetized rats. The c-Fos immunoreactivity in the six different NST areas along the rostral-caudal axis and six subregions in each of bilateral NST were compared between applications of distilled water and different concentrations of NaCl to the tongue of experimental animals. From this study, salt stimulation with high concentration (1.0 M NaCl) induced significantly higher c-Fos expression in intermediate NST and dorsal-medial and dorsal-middle subregions of the NST compared to distilled water stimulation. The result represents the specific spatial distribution of salt taste perception in the NST.     

Effects of Acupuncture Stimulation at Different Acupoints on Formalin-Induced Pain in Rats

Acupuncture is the process of stimulating skin regions called meridians or acupoints and has been used to treat pain-related symptoms. However, the pain-relieving effects of acupuncture may be different depending on acupoints. In the present study, the effects of acupuncture on behavioral responses and c-Fos expression were evaluated using a formalin test in male Sprague-Dawley rats in order to clarify the analgesic effects of three different acupoints. Each rat received manual acupuncture at the ST36 (Zusanli), SP9 (Yinlingquan) or BL60 (Kunlun) acupoint before formalin injection. Flinching and licking behaviors were counted by two blinded investigators. Fos-like immunoreactivity was examined by immunohistochemistry in the rat spinal cord. Manual acupuncture treatment at BL60 acupoint showed significant inhibition in flinching behavior but not in licking. Manual acupuncture at ST36 or SP9 tended to inhibit flinching and licking behaviors but the effects were not statistically significant. The acupuncture at ST36, SP9, or BL60 reduced c-Fos expression as compared with the control group. These results suggest that acupuncture especially at the BL60 acupoint is more effective in relieving inflammatory pain than other acupoints.     

Dosage-Dependent Impact of Acute Serotonin Enhancement on Transcranial Direct Current Stimulation Effects

BackgroundThe serotonergic system has an important impact on basic physiological and higher brain functions. Acute and chronic enhancement of serotonin levels via selective serotonin reuptake inhibitor administration impacts neuroplasticity in humans, as shown by its effects on cortical excitability alterations induced by non-invasive brain stimulation, including transcranial direct current stimulation (tDCS). Nevertheless, the interaction between serotonin activation and neuroplasticity is not fully understood, particularly considering dose-dependent effects. Our goal was to explore dosage-dependent effects of acute serotonin enhancement on stimulation-induced plasticity in healthy individuals.MethodsTwelve healthy adults participated in 7 sessions conducted in a crossover, partially double-blinded, randomized, and sham-controlled study design. Anodal and cathodal tDCS was applied to the motor cortex under selective serotonin reuptake inhibitor (20 mg/40 mg citalopram) or placebo medication. Motor cortex excitability was monitored by single-pulse transcranial magnetic stimulation.ResultsUnder placebo medication, anodal tDCS enhanced, and cathodal tDCS reduced, excitability for approximately 60–120 minutes after the intervention. Citalopram enhanced and prolonged the facilitation induced by anodal tDCS regardless of the dosage while turning cathodal tDCS-induced excitability diminution into facilitation. For the latter, prolonged effects were observed when 40 mg was administrated.ConclusionsAcute serotonin enhancement modulates tDCS after-effects and has largely similar modulatory effects on motor cortex neuroplasticity regardless of the specific dosage. A minor dosage-dependent effect was observed only for cathodal tDCS. The present findings support the concept of boosting the neuroplastic effects of anodal tDCS by serotonergic enhancement, a potential clinical approach for the treatment of neurological and psychiatric disorders.     

Effects of Spontaneous Gastric Hypoacidity on the Pharmacokinetics of Zidovudine and Didanosine

Study Objective . To determine the effect of spontaneous gastric hypoacidity on the pharmacokinetics of zidovudine and didanosine in subjects infected with the human immunodeficiency virus (HIV). Design . Controlled, open-label, single-dose, pharmacokinetic study. Subjects . Thirty-two asymptomatic HIV-infected subjects. Interventions . Gastric pH studies were conducted in all 32 subjects, and 20 of these subjects (8 women, 12 men) were enrolled into the pharmacokinetic study. They were stratified into two groups according to fasting gastric pH: those without and with gastric hypoacidity (minimum gastric pH < 3 and ≥ 3, respectively). Gastric pH was measured using the Heidelberg pH monitoring system in all subjects before and during pharmacokinetic analysis of zidovudine 100 mg or didanosine 200 mg (given as two 100-mg tablets dissolved in 6 oz water). Plasma samples were collected over 8 hours after dosing. Measurements and Main Results . Six (20%) of 30 subjects had a minimum gastric pH of 3 or above on at least two occasions, and the remaining 2 had variable gastric pH. Although gastric pH was unchanged during the administration of zidovudine, it increased to greater than 9 in 11 of 12 subjects with didanosine, regardless of baseline value. For both drugs, there were no statistically significant differences in peak plasma concentration (C_max), time to reach peak plasma concentration (T_max), elimination rate constant (k_e), and area under the plasma concentration-time curve from time zero to infinity (AUC_0–∞) between subjects with and without gastric hypoacidity despite sufficient statistical power to detect a 56% difference in clearance for either drug (α 0.05, β 0.1). Conclusion . Gastric hypoacidity occurs in approximately 20% of HIV-infected patients and does not appear to influence zidovudine or didanosine pharmacokinetics.     

金丝桃甙对抗缓激肽、钾离子和组织胺致痛作用的实验研究

本文观察了缓激肽、钾离子、组织胺等诱致麻醉兔隐神经传入纤维放电的作用及金丝桃甙对上述致痛因子作用的影响。经股动脉注射缓激肽0.3μg/kg、1％KCl 0.25ml/kg、组织胺150μg/kg,均能显著诱发隐神经传入放电(比基础放电分别提高3.5、4.3、3.6倍,均为p<0.01);同一途径给予金丝桃甙10mg/kg,对缓激肽、组织胺作用的抑制率分别高达75.6％和90.8％;金丝桃甙5mg/kg对KCl作用的抑制率高达73.3％。金丝桃甙在给药后5分忡内即迅速起效并达作用高峰,维付45分钟以上。同法给予吗啡2mg/kg不能对抗缓激肽的作用。上述结果表明,金丝桃甙具有外周镇痛作用,它可能通过影响致痛因子对痛觉传入神经的激活过程发挥作用。     

Antagonism of Reserpine-Induced Suppression of Spontaneous Motor Activity by Stimulation of 5-HT1A Receptors in Rats

Abstract: The 5-HT_1A and the DA D₂ receptor agonists 8-OH-DPAT (0.05–3.2 mg kg^–1 subcutaneously, –20 min.) and quinpirole (0.08–1.25 mg kg^–1 subcutaneously, –20 min.), respectively, both partially antagonized reserpine-induced (5 mg kg^–1 subcutaneously, –16 hr) suppression of spontaneous motor activity in the rat. Four different aspects of the spontaneous motor activity were recorded in a photocell-equipped open-field (8x8 photocells, 90 mm apart, defining two horizontal planes): locomotor activity (all photocell counts at the lower level); rearing (all photocell counts at the upper level); forward locomotion (the proportion movements across the arena); peripheral activity (the proportion locomotor activity as picked up by the photocell beam closest to the wall, i.e. 25 mm). As denned by these variables, the pattern of activity produced by 8-OH-DPAT or quinpirole were indistinguishable, The effects produced by 8-OH-DPAT were fully antagonized by the 5-HT₁ antagonist (–) pindolol (4 mg kg^–1 subcutaneously, –30 min.), but not by the DA D₂ receptor antagonist raclopride (2 mg kg^–1 subcutaneously, –30 min.) nor by the 5-HT₂ receptor antagonist ritanserin (2 mg kg^–1 subcutaneously, –30 min.), whereas effects produced by quinpirole were fully antagonized by raclopride (2 mg kg^–1 subcutaneously, –30 min.). Effects produced by quinpirole, but not 8-OH-DPAT, were potentiated by administration of the DA D₁ agonist SKF-38,393 (3 mg kg^–1 subcutaneously, –20 min.). It is concluded that effects by 8-OH-DPAT on spontaneous motor activity in the reserpine treated rat primarily are due to stimulation of postsynaptic 5-HT_1A receptors.     

布托啡诺和芬太尼伍用异丙酚后对自主呼吸的影响

目的:观察布托啡诺和芬太尼伍用异丙酚后对自主呼吸的影响。方法:选择80例门诊择期行肠镜检查的患者,随机分成2组,A组布托啡诺+异丙酚,B组芬太尼+异丙酚。记录不同时段的循环体征、呼吸参数和听觉诱发电位,同时记录不良反应及药物用量。结果:在麻醉深度相同的情况下,2组血压、脉搏差异无统计学意义。2组患者的1～5min通气量均明显低于基础值,而芬太尼使这一趋势更加明显。B组发生的呼吸系统问题明显高于A组。结论:布托啡诺对自主呼吸抑制较轻微,不良反应少,是一种适用于门诊短小手术的麻醉药品。