β-内啡肽在中枢吗啡预处理减轻大鼠心肌缺血后损伤中的作用

目的观察中枢与外周β-内啡肽对缺血后心肌的影响及其在侧脑室吗啡预处理减轻大鼠心肌缺血/再灌注损伤中的含量变化,探讨β-内啡肽在中枢吗啡预处理在体大鼠缺血后心肌保护作用中的角色。方法66只♂SD大鼠,分别建立侧脑室微量注射和心肌缺血/再灌注损伤动物模型。随机分为假手术(Sham)组、缺血对照(CON)组、缺血预处理(IPC)组、中枢和外周β-内啡肽激动剂(Icv/Iv-EP)组、中枢吗啡预处理(MPC组)、中枢β-内啡肽阻断剂(Icv-MPC-Anti-EP/Icv-Anti-EP-MPC)组、外周β-内啡肽阻断剂(Icv-MPC+Iv-Anti-EP)组、中枢和外周β-内啡肽阻断剂自身对照(Icv/Iv-Anti-EP)组。观察平均动脉压(MAP)、心率(HR)、压力心率乘积(RPP)、缺血危险区(AAR)、梗死区(IS)体积、IS/AAR等的变化;同时以免疫组化观察下丘脑弓状核(arcuate nucleus,ARC),中脑导水管周围灰质(periaque-ductalgray,PAG)及左室心肌(myocardium of left ventricle,MC)β-内啡肽的阳性表达。结果与CON组相比,IPC、MPC、Icv-EP、Iv-EP、Icv-Anti-EP-MPC、Icv-MPC+Iv-Anti-EP组均明显降低IS/AAR(P<0.01);Icv-MPC-Anti-EP组虽然取消MPC的保护效应(P<0.01),但较CON组差异仍有统计学意义(P<0.05);与CON组相比,MPC组减弱了ARC中β-内啡肽的阳性表达(P<0.05),同时明显增强PAG和左室心肌的免疫反应强度(P<0.05;P<0.01)。结论中枢与外周β-内啡肽对缺血后心肌损伤有保护作用;侧脑室吗啡预处理后可能促进下丘脑弓状核释放β-内啡肽,后者作为神经递质部分参与了中枢吗啡预处理介导的心肌保护效应。     

左旋千金藤立定和DA受体激动剂对6-OHDA损毁大鼠旋转行为和基底核神经元放电的作用部位(英文)

目的:确定l-SPD在基底神经核的作用部位。方法:6-OHDA损毁大鼠单侧黑质致密区(SNC),核团内微注或微电泳给予l-SPD或DA激动剂,作旋转实验和神经元放电记录。结果:1)大鼠纹状体损毁侧DA免疫反应物减少。2)新纹状体或黑质网质区(SNR)内微注DA激动剂Apo(D_1/D_2),SK＆F38393(D_1)或SPD引起大鼠强烈旋转,而微注Ly171555(D_2)于SNR或DA激动剂和l-SPD于苍白球(GP)均不引起旋转。卡英酸进一步损毁GP或脚间核(EP),DA激动剂或l-SPD诱发大鼠旋转显著下降。3)微电泳Apo或SPD引起SNR神经元放电,但对GP神经元无效。结论:l-SPD诱发大鼠旋转和神经元放电由D_1受体介导,基底核新纹状体和SNR是其作用部位,而不是GP。通过SNR的直接环路在旋转行为中起重要作用。     

β-内啡肽对谷氨酸神经毒性作用的影响

采用形态学观察、β-内啡肽(β-End)放射免疫测定及单细胞内游离钙浓度——[Ca²⁺]i检测等方法,观察了β-End对谷氨酸单钠(MSG)诱发神经元损伤的影响,分析了可能的作用机制。结果表明,β-End可以明显加重MSG诱发的下丘脑弓状核神经元的损伤;β-End和MSG诱发的[Ca²⁺]i增高可被维拉帕米部分逆转。另外,吗啡可以进一步加剧MSG诱导的各脑区β-End含量的变化。提示β-End可以明显地加剧MSG的神经毒性作用,其机制与MSG能诱发脑内β-End的含量的增多及β-End可进一步破坏MSG引起的胞内钙稳态失衡有关。     

Involvement of medulary tail-flick related neurons in descending facilitation evoked by chemical stimulation of rat lateral habenular nucleus

研究外侧缰核内微量注射Ｌ谷氨酸钠对大鼠延髓甩尾相关神经元活动和甩尾反射的影响．方法：用辐射热烫尾并同步记录延髓头端腹内侧区神经元单位放电和甩尾反射．结果：外侧缰核内微量注射Ｌ谷氨酸钠可加强给型甩尾相关细胞自发放电，抑制撤型甩尾相关细胞的自发放电，两类细胞的自发放电率分别从注射前的５８±２２Ｈｚ和１１．８±２２Ｈｚ变为注射后的１０９±３４Ｈｚ和６１±２２Ｈｚ．同时易化了两类细胞的甩尾相关反应和伤害剌激引起的甩尾反射，甩尾反射潜伏期从注射前的４０４±０１７ｓ缩短为注射后的２９７±０１３ｓ．结论：外侧缰核对节段性防御反射有下行易化作用，这种易化作用是通过延髓内撤型和给型甩尾相关细胞的协同活动而实现的．     

家兔隔区和伏核内钙、镁离子对抗电针镇痛与吗啡镇痛

本文通过脑内慢性埋植套管向家兔一侧隔区或伏核内注射微量(10 nmol)CaCl_2或MgCl_2,可显著对抗吗啡镇痛和电针镇痛。注入核外则无效。家兔一侧隔区或伏核内注入阳离子螯合剂CDTA(20 nmol)加强吗啡镇痛和电针镇痛。文中就Ca~(2 ),Mg~(2 )作用的相似性,电针镇痛与吗啡镇痛机理的相似性,以及伏核和隔区在上述镇痛中的重要性进行了讨论。     

Effect of tetrahydropalmatine analogs on Fos expression induced by formalin pain 1

目的：研究四氢巴马汀（ＴＨＰ）同类物对福尔马林致痛诱导的Ｆｏｓ蛋白表达的影响,以阐明ＴＨＰ同类物的镇痛机制．方法：在右后肢脚掌皮下注射５％福尔马林５０μＬ,诱发炎性疼痛,用免疫组织化学方法观察Ｆｏｓ蛋白表达．结果：腹腔注射ＴＨＰ同类物和Ｄ２受体拮抗剂螺哌隆诱导的Ｆｏｓ蛋白表达主要位于纹状体和伏膈核．Ｄ２受体激动剂喹吡罗可阻滞ｌＴＨＰ和螺哌隆诱导的Ｆｏｓ蛋白表达．ＴＨＰ同类物明显增加脑干下行痛觉调制系统的Ｆｏｓ蛋白表达,并能明显抑制福尔马林诱导的脊髓背角浅层和深层的Ｆｏｓ蛋白表达．结论：ＴＨＰ同类物通过阻滞纹状体和伏膈核的Ｄ２受体,加强脑干下行痛觉调制系统的功能,抑制外周痛觉信息在脊髓水平的传入,达到它们的镇痛作用．     

褪黑素对损毁弓状核大鼠所致肥胖的干预研究

目的 观察褪黑素对损毁弓状核大鼠所致肥胖的干预作用.方法 皮下注射谷氨酸钠,建立大鼠弓状核损毁所致中枢性肥胖,比较各组大鼠体质量指数(BMI) ;测定体温变化、摄食量和脂肪重;检测甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)等和血压;观察弓状核病理学变化.结果 褪黑素处理肥胖大鼠后,体温逐渐升高,其中高、低剂量给药组大鼠的BMI均明显回降(P<0.05,P<0.01),血压降低(P<0.01,P<0.05).褪黑素高、低剂量组大鼠体内白色脂肪重量,较模型组明显降低(P<0.01,P<0.05),棕色脂肪量明显增多(P<0.05,P<0.01).甘油三酯、高密度脂蛋白和低密度脂蛋白含量,褪黑素治疗组明显降低(P<0.01).结论 褪黑素对损毁大鼠弓状核所致肥胖具有干预作用,可能是由于其使能量消耗增多对肥胖有一定的抵抗作用.     

脊髓以上多巴胺D_2受体介导左旋四氢巴马汀的镇痛作用

目的:研究DA受体与左旋四氢巴马汀(l-THP)镇痛作用的关系,以阐明l-THP的镇痛机制。方法:腹腔(ip)与鞘内(ith)给药,以大鼠甩尾反应观测热伤害性致痛阈。结果:ip l-THP或D_2受体拮抗剂螺哌隆产生剂量依赖性镇痛效应,并能被D_2受体激动剂喹吡罗翻转,但不被纳洛酮翻转。而ithl-THP或螺哌隆无镇痛效应,但它们能拮抗ith喹吡罗引起的镇痛效应。结论:激动脊髓D_2受体或阻滞脊髓以上水平D_2受体均产生镇痛效应;l-THP镇痛作用通过阻滞脊髓以上D_2受体实现。     

D-半乳糖对大鼠下丘脑弓状核神经元超微结构的影响

目的:观察D-半乳糖对大鼠下丘脑弓状核超微结构的影响。方法:12只6月龄大鼠随机分成2组,对照组和D-半乳糖组,对照组每天皮下注射生理盐水,D-半乳糖组每天皮下注射D-半乳糖,剂量为100 mg.kg-1,连续给药3个月后,在全麻下,心脏放血处死大鼠,立即从左心室灌注2.0%~2.5%多聚甲醛-戊二醛的固定液50 mg.kg-1,并完整取出脑,放入2.5%戊二醛溶液中后固定,根据脑定位图谱取出大鼠弓状核,最后将取出组织块制成超薄切片在电镜下进行观察。结果:与对照组大鼠相比,D-半乳糖组大鼠弓状核神经元表现出衰老样变化,部分神经元细胞胞浆内细胞器明显减少,胞体减小,脂褐素增多,并观察到典型的胞核染色质边聚的凋亡神经元和轴突明显萎缩的老化神经元,而对照组大鼠神经元没有观察到明显的结构变化,胞浆中含有丰富的细胞器。结论:D-半乳糖可导致大鼠下丘脑弓状核发生衰老样变化,神经元发生萎缩和凋亡。     

介导单针吗啡诱导行为敏化新的脑区——隔核

目的单针吗啡诱导的行为敏化是研究阿片类药物成瘾神经可塑性变化的重要动物模型。目前认为隔核是脑内与奖赏、学习和记忆等关系较为密切的核团之一。因此,本研究将探讨隔核在单针吗啡诱导的行为敏化中的作用,并初步解析其作用机制。方法和结果通过旷场实验发现,单针吗啡(第1天:3～-30 mg·kg-1,sc)预处理的大鼠在吗啡(第8天:3 mg·kg-1,sc)激发时表现出高活动性,也就是行为敏化反应;在敏化实验前进行双侧隔核电损毁手术,发现大鼠对吗啡的行为敏化反应消失,但对吗啡的急性反应不受影响;而在单针吗啡预处理之后立即进行双侧隔核电损毁,发现7 d后大鼠在吗啡激发时仍表现出行为敏化;此外,通过条件性位置偏爱实验和甩尾实验,分别评价了吗啡在隔核损毁大鼠中的奖赏与镇痛作用;为了进一步明确隔核参与行为敏化的过程,按照侧隔核与中隔核的分区,分别通过核团内微量注射吗啡的方法建立行为敏化。发现预处理时在侧隔核或中隔核给于吗啡(30μg/rat)能使大鼠在激发后(3mg·kg-1,sc)出现行为敏化;预处理前,在侧隔核或中隔核内给与利多卡因(10μg/rat)或mu受体拮抗剂β-FNA(2μg/rat)能抑制行为敏化的建立。结论在吗啡预处理前,隔核损毁或者阻断隔核内阿片受体能抑制行为敏化的建立,说明隔核是参与单针吗啡诱导行为敏化形成期的关键性核团,并且侧隔核与中隔核的mu受体可能是这一过程的作用靶点。     

四氢巴马汀同类物对福尔马林致痛诱导Fos蛋白表达的影响

目的 研究四氢巴马汀（ＴＨＰ）同类物对福尔马林致痛诱导的Ｆｏｓ蛋白表达的影响,以阐明ＴＨＰ同类物的镇痛机制。方法 在右后肢脚掌皮下注射５％福尔马林５０μＬ,诱发性疼痛,用免疫组织化学方法观察Ｆｏｓ的蛋白表达,结果：腹腔注射ＴＨＰ同类物和Ｄ２受体拮抗剂螺哌隆诱导的Ｆｏｓ蛋白表达主要位于纹状体和伏膈核,Ｄ２受体激动剂喹吡罗可阻滞ｌ－ＴＨＰ和螺哌隆诱导的Ｆｏｓ蛋白表达,ＴＨＰ同类物明显增加脑干下行痛觉调     

乙醇促进大鼠纹状体隔核抗坏血酸的释放

应用脑内微透析技术结合ＨＰＬＣ－ＥＣＤ法检测显示，乙醇（２．５，５．０ｇ·ｋｇ－１，ｉｐ）显著增加大鼠纹状体和伏隔核抗坏血酸的释放。５．０ｇ·ｋｇ－１乙醇可使纹状体和伏隔核释放峰值达３０％以上，对伏隔核抗坏血酸的影响持续时间长于纹状体。提示脑中抗坏血酸参与乙醇对中枢神经系统的作用。     

Definition of the in-vivo accumulation of [3H]spiperone in brain using haloperidol and sulpiride to determine functional dopamine receptor occupation

The in-vivo administration of [3H]spiperone caused an accumulation of radioactivity in the substantia nigra, tuberculum olfactorium, nucleus accumbens, striatum and frontal cortex when compared with cerebellar levels. Haloperidol (0.01-1.0 mg kg-1 i.p.) dose-dependently prevented the accumulation of [3H]spiperone in the substantia nigra, tuberculum olfactorium, striatum and nucleus accumbens. Sulpiride (10-160 mg kg-1 i.p.) dose-dependently prevented the accumulation of [3H]spiperone only in the substantia nigra. The effects of sulpiride on other areas were not consistent; there was a suggestion of a reduction in the accumulation of [3H]spiperone in tuberculum olfactorium and striatum, but not in nucleus accumbens. Neither haloperidol (0.01-1.0 mg kg-1 i.p.) nor sulpiride (10-160 mg kg-1 i.p.) caused displacement of [3H]spiperone from the frontal cortex. Both haloperidol (0.01-0.5 mg kg-1) and sulpiride (10-80 mg kg-1) increased striatal and mesolimbic HVA concentrations. Haloperidol potently blocked apomorphine-induced stereotypy but sulpiride was only effective at the highest dose employed. The functional effect produced by haloperidol correlated with its ability to define [3H]spiperone binding in-vivo to dopamine receptors in the substantia nigra, striatum and tuberculum olfactorium. In contrast, there was no correlation between functional effect of sulpiride and its ability to define [3H]spiperone binding in-vivo.     

褪黑素对大鼠下丘脑弓状核前阿黑皮素mRNA表达的影响(英文)

目的:观察外源性给予褪黑素对大鼠下丘脑弓状核内神经细胞的前阿黑皮素(POMC) mRNA表达水平的影响。方法:实验大鼠分给药组及对照组,给药组大鼠间隔12 h腹腔注射褪黑素2次(9∶00 am,9∶00pm),每次剂量90mg·kg~(-1),对照组大鼠注射配药液。最后一次注射后12 h,灌注取脑、冰冻切片,进行原位杂交实验,计算机图像处理技术测定染色脑片积分光密度(IOD)值、平均光密度(OD)值。结果:给药组大鼠下丘脑弓状核内POMC mRNA表达明显增强;其IOD和OD值均显著增加。结论:褪黑素可加强大鼠弓状核内POMC mRNA的表达。     

Inhibitory effect of crotoxin on the pain-evoked discharge of neurons in thalamic parafascicular nucleus in rats.

Crotoxin (Cro), the principal neurotoxic component of Crotalus durissus terrificus, has been previously reported to have a behavioral analgesic effect in rats and mice. The present study investigated electrophysiologically the effect of Cro on pain-evoked unit discharge of neurons in thalamic parafascicular nucleus (Pf) and underlying mechanisms of its effect. The electrical discharge of Pf neurons was recorded with the microelectrode technique in rats. Intracerebroventricular (i.c.v.) injection of Cro at 0.25, 0.45 and 0.65 microg/kg resulted in a dose-dependent inhibitory effect on the pain-evoked discharge of Pf neurons. The discharge frequency and the discharge duration significantly (P<0.05) decreased after Cro administration. This inhibitory effect was significantly (P<0.05) attenuated after pretreatment with para-chlorophenylalanine (pCPA), or electrolytic lesion of dorsal raphe (DR) nucleus. In contrast, i.c.v. injection of atropine (muscarinic receptor antagonist, 5 microg) or naloxone (opioid receptor antagonist, 4 microg) had no effect on Cro-induced inhibition of discharge of Pf neurons. The results suggested that Cro has an analgesic effect, which is mediated, at least partially, by the central serotonergic system.     

The contrasting effects of neuroleptics on transmitter release from the nucleus accumbens and corpus striatum

The effects of haloperidol, chlorpromazine and clozapine on transmitter release have been studied by measuring the simultaneous release of dopamine and acetylcholine from tissue slices of nucleus accumbens and striatum in vitro following in vivo drug application, either a single dose or daily for periods of up to 25 days. In the striatum, both single and chronic injections of haloperidol (1 and 2 mg. kg-1) caused a large and significant enhancement (up to 83%) of the K+-evoked release of [3H]acetylcholine synthesized from [3H]choline. In contrast, in the nucleus accumbens, the K+-evoked release of [3H]acetylcholine was not significantly affected by neuroleptics when compared with the controls which received injection of vehicle. Clozapine (50 mg.kg-1) also enhanced the K+-evoked release of [3H]acetylcholine relative to the resting release but the effect was smaller than that with haloperidol or chlorpromazine. The evoked release of preloaded [14C]dopamine from either nucleus accumbens or striatum was unaffected by treatment with haloperidol. However, chlorpromazine (25 mg.kg-1) and clozapine (50 mg.kg-1) significantly enhanced the evoked release of preloaded [14C]dopamine from tissue slices of striatum. A similar but reduced effect of enhancing release was also seen in the nucleus accumbens in response to chlorpromazine. In support of these results, dopamine itself applied in vitro induced an opposite effect to that of the neuroleptics. Thus in the striatum, dopamine (4 x 10(-4) M) markedly reduced the release of [3H]acetylcholine (45%). A smaller inhibition was also seen in the nucleus accumbens (25%).     

Effects of acute and chronic clozapine on dopamine release and metabolism in the striatum and nucleus accumbens of conscious rats.

1. The effect of single and repeated (once daily for 23 days) oral doses of 20 and 60 mg kg-1 clozapine on dopamine release and metabolism were studied by intracerebral dialysis in the striatum and nucleus accumbens of conscious rats. 2. The basal output of dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum and nucleus accumbens of rats given clozapine 20 or 60 mg kg-1 chronically, measured one day after the last drug dose, was not significantly different from that of vehicle-treated animals. 3. Challenge doses of 20 or 60 mg kg-1 clozapine produced similar increases in dopamine levels in the striatum and nucleus accumbens of animals which had received vehicle or clozapine 20 or 60 mg kg-1 once daily for 23 days, except that 1 h after administration 60 mg kg-1 clozapine had a greater effect in the nucleus accumbens. 4. In animals treated chronically with clozapine 20 and 60 mg kg-1 or vehicle, DOPAC levels in the striatum and nucleus accumbens were increased to the same extent by challenge doses of clozapine (20 or 60 mg kg-1). In animals treated chronically with clozapine, a challenge dose of 60 mg kg-1 had significantly greater effect on HVA only in the nucleus accumbens. 5. When DOPAC and HVA were measured post mortem in the striatum and nucleus accumbens 2 h after various oral doses of clozapine, it was found that 10 mg kg-1 significantly increased dopamine metabolites only in the nucleus accumbens whereas 100 mg kg-1 had this effect in both regions.(ABSTRACT TRUNCATED AT 250 WORDS)     

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     

孕酮对吗啡条件性位置偏爱大鼠相关脑区中枢多巴胺D2受体水平的影响

目的观察孕酮对于吗啡所致奖赏效应及相关脑区中D2受体水平的影响。方法 32只SD大鼠随机分为空白对照组、吗啡组、孕酮组和孕酮加吗啡组,建立吗啡条件性位置偏爱(CPP)模型,采用免疫组化法测定大鼠伏隔核、腹侧被盖区和纹状体D2受体的水平。结果与空白对照组比较,5mg·kg-1吗啡可诱导大鼠产生稳定的CPP效应(P<0.01),15mg·kg-1孕酮虽自身不能产生CPP效应,但与吗啡合用时能抑制吗啡CPP效应的获得。与空白对照组比较,吗啡组大鼠伏隔核、腹侧被盖区和纹状体中D2受体的平均光密度值降低(均为P<0.01)。与吗啡组比较,合用15mg·kg-1孕酮可使伏隔核和纹状体中D2受体的平均光密度值升高(P<0.01和P<0.05),而在腹侧被盖区中未见变化。结论孕酮可以有效抑制吗啡CPP效应,其机制可能与其逆转吗啡诱导的伏隔核和纹状体中D2受体水平的变化有关。