四氢巴马汀对大鼠伏核单位放电的影响

用清醒制动大鼠记录了前脑伏核神经元的自发放电。伏核单位放电率为4.9次/s。四氢巴马汀(THP)明显抑制伏核单位放电。抑制效应在给药后10 min开始,30 min时最明显。单胺氧化酶抑制剂优降宁对伏核放电无明显影响,但能消除THP对伏核放电的抑制作用。本研究结果和THP排空单胺介质的生化资料结果一致,可以认为THP为利血平样作用的单胺排空剂。     

阿托品对褪黑素抑制猫丘脑后核群诱发放电的影响

目的研究M受体阻断剂阿托品对褪黑素(melatonin,MT)中枢镇痛作用的影响,进一步探索MT的作用机制。方法采用猫脑立体定位技术和玻璃微电极细胞外记录法,以刺激内脏大神经(GSN)诱发猫丘脑后核群(PO)单位放电为内脏痛指标,侧脑室给药,观察药效。结果0.1% MT(10 μg·kg^-1,icv)可明显抑制刺激GSN在PO诱发的单位放电,0.1%阿托品(20 μg,icv)可拮抗其对PO短潜伏期(58±22) ms诱发放电的抑制作用,而0.1%吗啡(5 μg,icv)对此潜伏期放电的抑制作用则不被等量的阿托品拮抗。结论MT有中枢镇痛作用,在此过程中可能有胆碱能神经的参与,MT的镇痛机制与吗啡存在着差异。     

L-四氢巴马汀对羟考酮依赖大鼠不同脑区单胺递质水平的影响

目的：观察L-四氢巴马汀（L-THP）对羟考酮依赖大鼠不同脑区单胺递质含量的影响，探讨L—THP对抗羟考酮依赖的机制。方法：以连续递增给药建立羟考酮依赖大鼠模型，L—THP伴随给药，采用HPLC—ECD法测定大鼠前皮层、海马、纹状体和伏隔核内多巴胺（DA）和5-羟色胺（5-HT）含量的变化。结果：与空白对照组相比，羟考酮依赖的大鼠纳络酮催促戒断后前皮层内DA、高香草酸（HVA）和5-HT含量明显降低，伏隔核内DA、3，4-二羟基苯醋酸（DOPAC）、HVA和5-HT含量明显降低，海马内DA、DOPAC、5-HT含量没有明显变化，而5-吲哚乙酸（5-HIAA）明显升高，纹状体内DA及其代谢产物DOPAC、HVA以及5-HT、5-HIAA含量明显降低；L—THP（10，20，30mg·kg^-1，ig）伴随给药，能不同程度抑制上述变化。结论：L—THP可抑制羟考酮依赖引起的不同脑区内单胺类递质含量的变化，提示LTHP对抗羟考酮依赖可能与调节多巴胺和5-HT系统相关。     

纳络酮对褪黑素抑制猫丘脑后核群诱发放电的影响

目的研究阿片受体阻断剂纳络酮对褪黑素 (melatonin ,MT)中枢镇痛作用的影响 ,进一步探索MT的作用机制。方法采用猫脑立体定位技术和玻璃微电极细胞外记录法 ,以刺激内脏大神经(GSN)诱发猫丘脑后核群 (PO)单位放电为内脏痛指标 ,侧脑室给药 ,观察药效。结果侧脑室注射(icv) 4 3 0× 1 0 -3 mol·L-1MT 1 0 μg·kg-1可明显抑制刺激GSN在PO诱发的单位放电 ,2 75×1 0 -3 mol·L-1纳络酮 (5 0 μg,icv)可部分拮抗MT对PO诱发放电的抑制作用。结论MT有中枢镇痛作用 ,MT的镇痛作用与增加内源性阿片系统的活动有关     

七十味珍珠丸对脑损伤大鼠脑内单胺类神经递质的影响

通过对脑损伤大鼠脑内单胺类神经递质含量的测定,研究七十味珍珠丸治疗脑血管疾病的作用机理.ig给药后,制成脑损伤病理模型,采用荧光分光光度法检测脑内5-羟色胺(5-HT)、去甲肾上腺素(NA)、多巴胺(DA)含量.结果七十味珍珠丸显著降低脑损伤所致大鼠脑内5-HT,NA含量升高,对DA含量的抑制,也有一定作用趋势.     

去甲肾上腺素对吗啡依赖大鼠中枢痛觉的调制

目的研究去甲肾上腺素(NE)和酚妥拉明对吗啡依赖大鼠伏核(NAc)内痛兴奋神经元(PENs)和痛抑制神经元(PINs)生物电活动的影响。方法采用NAc内给药的方法,以电脉冲刺激右侧的坐骨神经作为伤害性刺激,用玻璃微电极记录吗啡依赖大鼠NAc内PENs或PINs的电变化。结果 NAc内微量注入NE(4 g.L-1,0.5μl)可使吗啡依赖大鼠NAc中PEN对伤害性刺激反应的痛诱发放电频率减少,潜伏期延长,但PIN痛诱发放电频率增加,抑制时程(ID)缩短,呈现出NE的镇痛效应。NAc内注入酚妥拉明(4g.L-1,0.5μl)产生相反反应,表明酚妥拉明可阻断内源性NE的作用。结论 NE和α-肾上腺素能受体均参与吗啡依赖大鼠NAc内伤害性信息的调控。NAc是调制吗啡依赖大鼠中枢痛觉的重要核团之一。     

三种浓度的酒精对大鼠伏核神经元传入电活动的抑制作用

目的··:研究酒精对伏核神经元的影响 ,初步探讨酒精依赖的生物学机制。方法 :·· 以两倍阈强度电刺激大鼠脑片嗅结节区 ,记录伏核神经元的传入电活动 ,观察3种浓度的酒精对该传入电位的影响 ,并分析了44mmol·L-1 的酒精对此传入电位的时间 -强度变化曲线。结果··:(1)酒精能降低伏核神经元传入电位的幅值 ;(2)44mmol·L -1酒精对伏核神经元传入电位的抑制作用最强 ;(3)44mmol·L-1 的酒精在作用9 -17min时发挥了最大抑制作用。结论·· :酒精能抑制伏核神经元的传入电活动 ,且此作用可能与酒精依赖的形成有关     

DL-四氢巴马汀对大鼠单胺的排空作用

DL-四氢巴马汀(THP)是中药延胡索的有效成分,具有镇静、安定、镇痛和温和降压等作用。本文用高压色谱并用电化学检测器法研究了THP对大鼠单胺代谢的影响。THP60mg/kg能降低三种单胺介质的含量:DA(-70%),NA(-50%),5-HT(-30%)。它们的酸性或中性代谢物HVA,DOPAC,MHPG-SO₄和5-HIAA含量显著升高(+200～300%)。而DA的甲基化代谢物3-甲氧基酪胺(3-MT)含量明显减少。DA酸性代谢物的升高和DA被COMT甲基化的代谢物3-MT的降低,皆表示DA被排空和导致DA能系统功能的低落。可以得出结论,THP是一个短效单胺排空剂。     

脑神经炎症对小鼠运动疲劳的影响及其可能机制

目的 研究脑神经炎症状态与运动疲劳之间的关联，并从脑能量代谢角度探讨其可能机制。方法 实验采用雄性C57BL/6J小鼠。(1)小鼠分为溶剂对照和脂多糖（LPS）组（每只小鼠2.5μg）、米诺环素组（每只小鼠12μg）、AZD3965组（每只小鼠50 nmol）或4-CIN组（每只小鼠40 nmol），每组12只，LPS侧脑室注射（icv）给药12 h，米诺环素、AZD3965和4-CIN组分别icv给药后30 min进行小鼠转棒实验，测定小鼠在棒时间。(2)小鼠分为溶剂对照和米诺环素3个剂量组（每只小鼠3,6和12μg），每组12只，米诺环素icv给药后30 min进行小鼠跑台实验，测定小鼠运动持续时间和运动距离；或分为溶剂对照和米诺环素组（每只小鼠12μg），每组12只，米诺环素icv给药后30 min进行小鼠负重游泳实验，测定小鼠游泳持续时间。(3)小鼠分为溶剂对照、LPS（每只小鼠2.5μg）和LPS+米诺环素组（每只小鼠2.5μg+12μg），每组12只，LPS组为LPS icv给药后12 h、LPS+米诺环素组为icv给予LPS后12 h再icv给予米诺环素后30 min进行...     

染料木黄酮对大鼠下丘脑脑片室旁核神经元放电的影响(英文)

目的研究染料木黄酮(GST)在心血管中枢神经系统的作用。方法应用细胞外记录单位放电技术,在下丘脑脑片上观察GST对静息状态下的室旁核神经元放电的影响。结果①26个脑片分别灌流GST 10,50,100μmol·L~(-1)2 min,有25个脑片放电频率明显降低,且呈浓度依赖性;②用0.2 mmol·L~(-1) L-谷氨酸灌流脑片,7/7个脑片放电频率明显增加,表现为癫痫样放电,在此基础上加灌GST 50μmol·L~(-1)2 min,其癫痫样放电被抑制;③用G蛋白激活的内向整流型钾通道阻断剂四乙胺1 mmol·L~(-1)灌流脑片,约10 min后加入GST 50μmol·L~(-1),8/8个脑片的放电抑制效应被完全阻断;④用一氧化氮合酶抑制剂左旋硝基精氨酸甲酯50μmol·L~(-1)灌流脑片,7/7个脑片的放电频率增加,在此基础上加灌GST 50μmol·L~(-1)2 min,放电被抑制。结论GST可抑制下丘脑室旁核神经元自发放电,并抑制L-谷氨酸诱发的神经元癫痫样放电。这种抑制作用可能与激活G蛋白激活的内向整流型钾通道,促进K~+外流,从而引起细胞膜超极化有关;而与NO释放无关。GST可能通过降低心血管中枢的活动性而产生一定的心血管系统保护作用。     

THE DOPAMINE PRODRUG, GLUDOPA, DECREASES BOTH RENAL AND EXTRARENAL NORADRENALINE SPILLOVER IN CONSCIOUS RABBITS

1. Renal and total noradrenaline (NA) spillover rates were examined under control conditions and during graded infusions of gludopa (γ-l-glutamyl-l-dopa) in conscious rabbits. 2. Gludopa infusion at 25 and 100 μg/kg per min did not alter mean arterial pressure (MAP) and heart rate (HR), but had significant dose-related effects on the renal dopamine (DA) system. At the high dose there were pronounced increases in urinary DA excretion (>6000-fold) and renal DA content (> 100-fold); renal NA content doubled. 3. Renal venous DA increased after gludopa infusion, but arterial plasma DA concentrations were not significantly changed. Mean arterial plasma gludopa and l-dopa concentrations reached 890, 3190 ng/mL and 3, 10 ng/mL at low and high doses, respectively. 4. Gludopa resulted in a pronounced dose-dependent fall in renal NA spillover, which at 100 μg/kg per min accounted for almost half of the reduction in overall NA spillover rate. 5. The significant falls in renal and extrarenal NA spillover rate during gludopa infusion are consistent with suppression of renal and overall sympathetic activity. Gludopa-induced inhibition of renal NA spillover is likely to be due to the actions of DA generated in the kidney on presynaptic DA-2 and α-2 receptors. A central sympathoinhibitory mechanism may explain the reduced total NA spillover.     

Effects of four dopamine agonists on l-tetrahydropalmatine-induced analgesia and electroacupuncture analgesia in rabbits

The effects of icv 4 dopamine (DA) agonists on analgesia caused by iv l-tetrahydropalmatine (THP) 8 mg/kg or by electro-acupuncture (EA) were studied by using the potassium iontophoretic dolorimetry in rabbits. The results showed that both THP-induced analgesia and EA analgesia were markedly attenuated by icv of DA or apomorphine (Apo), 2 mixed D1/D2 agonists. Similar results were obtained when SKF-38393, a selective D1 agonist, was applied. On the contrary, quinpirole hydrochloride (Qui), a selective D2 agonist, was found to enhance the analgesic action of THP or EA. However, DA, Apo, SKF-38393 or Qui per se did not influence the baseline pain threshold. All these observations indicate that functional alterations in DA receptor activities may be involved in THP-induced analgesia and EA analgesia, in which D1 and D2 subtype receptors exert different roles.     

优降宁对四氢巴马汀排空大鼠脑内儿茶酚胺作用的影响

DL-Tetrahydropalmatine (THP) is an active principle found in the Chinese herb Corydalis ambigua. It possesses sedative and analgesic activities. THP had been reported to deplete dopamine (DA), noradrenaline (NA) and serotonin in rat brain. The effect of reserpine in reducing the transmitters and its sedative action could be reversed by MAOI i. e. reserpine-reversal. In order to investigate the influence of pargyline on THP induced depletion of catecholamines, NA, DA and their metabolites were measured by high performance liquid chromatography coupled with electrochemical detection. It was shown that the decrease of NA and DA concentrations in the limbic area was reversed by pretreatment with pargyline, whereas that in the striatal area returned to normal. From this study further evidence was obtained to support the hypothesis that THP is a monoamine depletor with reserpine-like action.     

优降宁对四氢巴马汀排空大鼠脑内儿茶酚胺作用的影响

dl-四氢巴马汀(dl-Tetrahydropalmatine,THP)是中药延胡索(Corydalis ambigua)的有效成分之一,有镇静、安定和镇痛作用。本文作者曾报道,THP有利血平样作用,能排空动物脑内多巴胺(DA)、去甲肾上腺素(NA)和5-羟色胺及心脏内的NA,提出THP为一短效单胺排空剂。众所周知,利血平类化合物的作用可为单胺氧化酶抑制剂(MAOI)所翻转。如在利血平以前给予MAOI,则前者的镇静作用翻转为兴奋,对单胺的排空作用亦被     

The Action of Dopamine on Arterial Blood Pressure in the Rat

The mean arterial blood pressure in conscious normotensive Sprague-Dawley rats was recorded by means of in-dwelling arterial catheters. Dopamine hydrochloride (DA) was infused intravenously from 0.04 μg/min. up to 0.22 μg/min. The infusions always resulted in a hypertensive reaction. Intravenous injections of DA (1–50 μg/kg) or noradrenaline bitartrate monohydrate (NA) (0.02–0.5 μg/kg) were given before and after phenoxybenzamine (PBZ) (5 mg/kg); protriptyline (PTP) (10 mg/kg) and nialamide (100 mg/kg). The DA injections alone resulted in a pressor action. PBZ blocked or considerably diminished the pressor action of DA. PTP did not result in a clear-cut augmentation of the blood pressure response to DA like that seen after the various equipotent NA doses tested. Furthermore, there was no prolongation of the duration of the pressor action of DA after PTP, though this was found after NA. Nialamide did not alter the magnitude of the pressor action of DA and NA. However, the hypertensive response of L-DOPA (25 mg/kg) was markedly augmented by pretreatment with nialamide (10 mg/kg).     

EFFECTS OF A CONTINUOUS INFUSION OF DOPAMINE ON THE VENTILATORY AND CAROTID BODY RESPONSES TO HYPOXIA IN CATS

1. We investigated how a continuous infusion of dopamine (DA; 5μg/kg per min), which is often used clinically, would affect the ventilation and carotid chemoreceptor neural activity in anaesthetized cats. 2. In anaesthetized, spontaneously breathing cats, tidal volume (Vt) and respiratory frequency (f) were continuously monitored at five levels of inspired oxygen (P10₂= 110,130, 150, 170, 760mmHg) during Da or saline infusion. Vt and f were sampled for 1 min after 3 min exposure to each level of P10₂. Time control study was also performed. 3. DA infusion significantly lowered V_T under both normoxia and hypoxia in seven of eight cats. Respiratory frequency was not affected by DA infusion. Depression of ventilation during post-hypoxic hyperoxia was augmented by DA infusion. Chemodenervntion abolished the ventilatory response to hypoxia and DA did not further affect the ventilatory response to hypoxia. 4. In a second group of artificially ventilated cats, carotid chemoreceptor neural activity was recorded at five levels of arterial oxygen tension. DA infusion significantly depressed carotid chemoreceptor neural activity during normoxia and hypoxia in six of seven cats. 5. These findings suggest that changes in ventilation during low dosage of DA infusion closely correlate with carotid body neural output. A predominant effect of this dosage of DA (5 μg/kg per min) was depression in the ventilatory response to hypoxia due to an inhibition of carotid body neural output.     

Comparison of the thermoregulatory responses to intracerebroventricularly injected dopamine,noradrenaline and 5-hydroxytryptamine in the goat

The thermoregulatory responses to dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT), injected into the third cerebral ventricle of goats at 20°C ambient temperature (T_a) or during cold exposure, were compared before and after pretreatment with the DA receptor blocker haloperidol or the 5-HT receptor blocker methysergide. At 20°C T_a, intracerebroventricular (i.c.v.) injection of DA (800 μg), NA (200 μg) or 5-HT (800 μg) induced a decrease in body temperature (T_b) and dilatation of the ear vessels. After DA and 5-HT, but not after NA, panting was observed. During cold exposure both DA and NA caused a suppression of shivering and a fall in T_b. Pretreatment with haloperidol (400 μg, i.c.v.) attenuated the thermoregulatory effects of i.c.v. DA other than the dilatation of the ear vessels at 20°C T_a. Haloperidol did not influence the responses after i.c.v. NA or 5-HT. Methysergide (1.0 mg, i.c.v.) blocked panting and attenuated the decrease in T_b caused by i.c.v. DA and 5-HT at 20°C T_a and blocked the peripheral vasodilatation caused by 5-HT but not the dilatation caused by DA. During cold exposure methysergide antagonized the thermoregulatory effects of DA, but not those of NA. I.c.v. injection of haloperidol (400 μg) or methysergide (1.0 mg) during heat exposure induced a decrease in panting and a rise in body temperature, which suggests that both DA and 5-HT have a physiological role in the mediation of heat loss in the goat. We conclude that in the central thermoregulatory system of the goat there are excitatory DA receptors in the pathway from heat sensors to heat loss effectors. Activation of these receptors by i.c.v. DA or by heat exposure results in a secondary release of 5-HT. Since the vasodilating effect of DA was not influenced by haloperidol or methysergide, this effect could be mediated by haloperidol-insensitive (possibly inhibitory) DA receptors on the pathway controlling peripheral vasomotor tone. The thermoregulatory effects of i.c.v. NA are probably mediated by inhibitory NA receptors on the pathway from cold sensors to heat production effectors.     

Pirarubicin-induced endothelium-dependent relaxation in rat isolated aorta.

The mechanism of relaxation produced by pirarubicin [(2"R)-4'-O-tetrahydropyranyladriamycin, THP] has been studied in rat isolated aorta. THP (1.5 x 10(-6)-4.5 x 10(-5) M) markedly relaxed contractions induced by noradrenaline (10(-7) M) in the aorta with endothelium, but not in that without endothelium. The relaxation induced by 1.5 x 10(-5) M THP was inhibited by methylene blue (5 x 10(-6) M), hydroquinone (10(-4) M), phenidone (5 x 10(-5) M), haemoglobin (10(-6) M) and p-bromophenacyl bromide (5 x 10(-5) M), but not by indomethacin (2.5 x 10(-5) M). The relaxation induced by THP (1.5 x 10(-7) -4.5 x 10(-5) M) was inhibited by NG-nitro-L-arginine (10(-5) M), but enhanced by superoxide dismutase (10 units mL-1) or by L-arginine (10(-2) M). However, the THP-induced relaxation was not inhibited by various receptor antagonists such as atropine (10(-6) M), cimetidine (10(-5) M), diphenhydramine (3 x 10(-6) M) and [D-Pro4, D-Trp7,9,10]-substance P(4-11) (1.5 x 10(-6) M). In fifteen anthracycline analogues, THP and 13-dihydropirarubicin (both with a tetrahydropyranyl group) produced endothelium-dependent relaxations. These results suggest that the THP-induced relaxation which is probably mediated by endothelium-derived relaxing factor (EDRF) was not produced by an activation of muscarine, histamine H1 or H2, or substance P receptor, and further that the tetrahydropyranyl group must play an important role in the THP-induced relaxation.