用跳台法和避暗法观察药物对学习和记忆获得的影响

采用跳台和避暗法，观察康维命（ＣＶＭ）对小鼠学习和记忆获得的影响。结果表明，ＣＶＭ能提高小鼠的学习和记忆获得能力。两种方法均可用于促进学习记忆试验新药品的筛选，跳台法可观察对学习和记忆获得的影响，避暗法仅可观察对记忆获得的影响     

谷氨酸钠对小鼠学习记忆功能的影响

目的探讨不同剂量谷氨酸钠对小鼠学习记忆功能的影响。方法 ICR小鼠80只随机分为4组,即正常对照组(20mL.kg-1)、谷氨酸钠小剂量组(0.375g.kg-1)、谷氨酸钠中剂量组(0.75g.kg-1)和谷氨酸钠大剂量组(1.5g.kg-1)。小鼠灌胃给予谷氨酸钠1h后,采用跳台法和避暗法测定谷氨酸钠对小鼠学习记忆功能改变的影响。结果在跳台实验和避暗实验中,与正常对照组比较,谷氨酸钠中剂量组(0.75g.kg-1)和大剂量组(1.5g.kg-1)的小鼠错误次数增加,潜伏期变短,并且随给药剂量增加而影响增大。结论谷氨酸钠对成年小鼠的学习记忆行为有抑制作用,且与剂量成正相关。     

抗衰灵口服液对小鼠学习记忆的改善作用

目的观察抗衰灵口服液对多种化学物质所致学习记忆障碍的影响。方法给予各种化学试剂造成小鼠学习记忆功能障碍 ,采用一次性被动回避反应跳台法和避暗法 ,以及方向辨别性水迷宫法观察受试药的改善作用。结果抗衰灵口服液能明显减少东莨菪碱所致获得性记忆障碍小鼠的错误次数、增强戊巴比妥钠引起的空间记忆障碍小鼠的学习记忆能力 ,对抗亚硝酸钠造成的小鼠记忆巩固不良和40 %乙醇引起的小鼠记忆再现障碍。结论抗衰灵口服液具有多方面改善智力的作用     

石菖蒲的促进小鼠学习记忆和提高耐缺氧力作用

采用一次性被动回避条件反应训练和多种缺氧模型、观察了石菖蒲水提醇沉液对小鼠学习记忆和抗缺氧的作用。结果表明石菖蒲(0.1g/10g、0.2g/10g 相当于 LD50的1/54、1/27)灌服能明显改善东莨菪碱,亚硝酸钠所致小鼠的记忆获得和巩固的障碍,也能明显改善亚硝酸钠,(?)化钾和结扎两侧颈总动脉所致小鼠的缺氧状态。     

石菖蒲的促进小鼠学习记忆和提高耐缺氧力作用

采用一次性被动回避条件反应训练和多种缺氧模型、观察了石菖蒲水提醇沉液对小鼠学习记忆和抗缺氧的作用。结果表明石菖蒲(0.1g/10g、0.2g/10g 相当于LD50的1/54、1/27)灌服能明显改善东莨菪碱,亚硝酸钠所致小鼠的记忆获得和巩固的障碍,也能明显改善亚硝酸钠,氰化钾和结扎两侧颈总动脉所致小鼠的缺氧状态。     

清醒小鼠反复脑缺血再灌注法致学习记忆障碍模型的建立

目的　建立一种清醒小鼠反复脑缺血再灌注致学习记忆障碍模型的方法。方法　采用清醒小鼠反复脑缺血再灌注及单次脑缺血再灌注手术方法 ,应用跳台法 ,避暗法 ,脑海马CA1区神经细胞计数等方法研究脑缺血再灌注对小鼠行为学 ,脑病理形态学的影响 ,并预防应用尼莫地平等药物研究了反复脑缺血再灌注造模方法的稳定性及可靠性。结果　与假手术组比较 ,反复脑缺血再灌注使小鼠出现明显的学习记忆功能障碍且比相同缺血时间的单次脑缺血再灌注造成的损伤更为明显 ,并使脑海马CA1区神经细胞数明显减少 ;尼莫地平等药物可不同程度地改善反复脑缺血再灌注致学习记忆障碍小鼠的学习记忆功能。结论　清醒小鼠反复脑缺血再灌注法是一种稳定可靠 ,简便易行的致学习记忆障碍的造模方法。     

地西泮对小鼠自主活动和学习记忆功能的影响

目的：观察不同剂量地西泮（Diazepam,D）对小鼠自主活动和学习记忆功能的影响。方法：昆明种小鼠120只,随机分成4组：生理盐水组（NS组）,地西泮0.5mg/kg组（D0.5组）,地西泮1.0mg/kg组（D1.0组）,地西泮2.0mg/kg组（D2.0组）,每组10只。观察不同剂量地西泮对小鼠自主活动计数、跳台法（step-down test）和避暗法（step-through test）的潜伏期和错误次数的影响。结果：与NS组比较,地西泮可剂量依赖性地减少小鼠自主活动次数计数,缩短跳台法和避暗法的潜伏期,增多错误次数。结论：地西泮能减少小鼠自主活动,抑制小鼠学习记忆功能,但在停药3d后此作用消失。     

丙泊酚对幼小鼠自主活动和学习记忆行为的影响

目的观察丙泊酚(Prof)对幼小鼠自主活动和学习记忆行为的影响,探讨其与GABAA受体的关系。方法 300只9～10日龄小鼠分为3大组,分别进行自主活动实验、避暗实验和跳台实验,各组小鼠ip Prof或NS 10 min后icv荷包牡丹碱(Bic)或人工脑脊液(aCSF)。测试最后一次给药后15、30、45和60 min小鼠5 min内活动次数;跳台仪和避暗仪记录小鼠步入、跳下的潜伏期和错误次数。结果与NS组比,Prof可减少小鼠自主活动次数;给Prof 24h后小鼠步入和跳下潜伏期缩短、错误次数增加(P<0.05)。Bic可增加Prof小鼠自主活动次数,延长其跳下和步入潜伏期,减少错误次数(P<0.05)。结论 Prof可减少幼小鼠自主活动次数,损害学习记忆能力,GABAA受体是其重要靶位。     

EFFECTS OF INTRAHIPPOCAMPAL INJECTIONS OF THE CHOLINERGIC NEUROTOXIN AF64A ON PRESYNAPTIC CHOLINERGIC MARKERS AND ON PASSIVE AVOIDANCE RESPONSE IN THE RAT

1. The effects of the intrahippocampal injection of ethylcholine mustard aziridinium ion (AF64A) on the following cholinergic markers were examined. 2. Bilateral injection of 10 nmol of AF64A into the dorsal hippocampus caused a loss of choline acetyltransferase (CAT) activity in the dorsal hippocampus, ventral hippocampus, cortex and striatum. 3. This treatment caused significant decreases in ACh contents in the dorsal hippocampus, ventral hippocampus and cortex, but not in the striatum. 4. The step-down latencies during the test trials of both 10 and 50 nmol AF64A-treated groups were significantly shorter than those of vehicle-treated groups. 5. None of the control animals stepped down to the large box where they had previously received a foot shock, but 40% of the 10 nmol and 60% of the 50 nmol AF64A-treated animals stepped down to the large box within 600 s. 6. These results indicate that AF64A treatment produces biochemical and functional deficits in the cholinergic neurons in the CNS.     

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.     

METHODS OF ASSESSING THE PERCUTANEOUS ABSORPTION OF VOLATILE CHEMICALS IN ISOLATED PERFUSED SKIN: STUDIES WITH CHLOROPENT AFLUOROBENZENE AND DICHLOROBENZENE

The experimental determination of dermal absorption of volatile chemicals is fraught with difficulties. The isolated perfused porcine skin flap (IPPSF) is a biologically intact, perfused skin preparation that has been employed to predict dermal absorption of chemicals in humans. The purpose of this work was to explore various experimental dosing strategies for volatile chemicals using dichlorobenzene (DCB) and chloropentafluorobenzene (CPFB) as model compounds. Effects of complete occlusion and various strategies of vapor trapping, vapor dosing, and solvent effects were explored. The results suggest that dosing methodology is a major determinant of dermal absorption and could easily skew results obtained from different systems. A biologically sensitive system such as the IPPSF is particularly sensitive to the manipulations required to ensure precise dosing of these compounds. An interesting finding was that the effects of solvents on compound absorption that are routinely described in liquid dosing scenarios were also detected when both the compound and solvent were exposed during the vapor phase.     

间硝苯吡啶与硝苯吡啶对离体心脏、血管钙拮抗作用的比较性研究

M-Nif对离体豚鼠左心房的钙拮抗作用PD_2~′=7.05较Nif PD_2~′=7.19弱,抑制心肌的IC_(50)=7.5×10~(-8)M亦较Nif IC_(50)=2.9×10~(-6)M弱2.6倍。在离体猪冠脉条实验中M-Nif PD_2~′=7.06,Nif PD_2~′=6.88,前者稍强,前者抑制血管的作用IC_(50)=6.166×10~(-7)M亦强于后者IC_(50)=7.02×10~(-7)M 114倍,Nif扩张血管作用较抑制心肌作用强10倍,提示M-Nif扩张血管与抑制心肌的宽度更大,对治疗心力衰竭、降压将更有利。     

间硝苯吡啶与硝苯吡啶对离体心脏、血管钙拮抗作用的比较性研究

M-Nif对离体豚鼠左心房的钙拮抗作用PD₂′=7.05较Nif PD₂′=7.19弱,抑制心肌的IC₅₀=7.5×10^-8M亦较Nif IC₅₀=2.9×10^-6M弱2.6倍。在离体猪冠脉条实验中M-Nif PD₂′=7.06,Nif PD₂′=6.88,前者稍强,前者抑制血管的作用IC₅₀=6.166×10^-7M亦强于后者IC₅₀=7.02×10^-7M 114倍,Nif扩张血管作用较抑制心肌作用强10倍,提示M-Nif扩张血管与抑制心肌的宽度更大,对治疗心力衰竭、降压将更有利。     

EFFECTS OF NEUROPEPTIDE Y ON THE PRESSOR RESPONSES TO PHENYLEPHRINE AND TO ACTIVATION OF THE SYMPATHETIC NERVOUS SYSTEM IN ANAESTHETIZED RATS

1. The effects of neuropeptide Y (NPY) on the pressor responses to intravenous injections of phenylephrine and to reflex activation of the sympathetic nervous system by stimulation of the sciatic nerve were examined in anaesthetized rats. 2. NPY (10-20 micrograms/kg) always potentiated the pressor response to exogenous phenylephrine (by a mean of 28.1 +/- 5.0%). The effect of the same dose of NPY on the pressor response to sciatic nerve stimulation was variable (sometimes inhibition, sometimes potentiation). 3. NPY appears to act by potentiating post-synaptic alpha-adrenoceptor-mediated vasoconstrictor effects. It may also inhibit noradrenaline release by a presynaptic action. Thus the net effect of NPY on sympathetic activation in vivo may depend on the balance between these two opposing actions.     

利血平与优降宁对动物痛阈和吗啡镇痛作用影响因素探讨

采用三种测痛方法,观察了利血平、优降宁对小鼠、大鼠正常痛阈和吗啡镇痛作用的影响,结果表明:ip利血平2 mg/kg,优降宁100 mg/kg均能明显抑制小鼠扭体反应;ip利血平1 mg/kg能明显提高小鼠热板反应时间,但ip优降宁75 mg/kg无明显影响;ip利血平6 mg/kg,优降宁75 mg/kg对大鼠甩尾反应时间均无明显影响;利血平(小鼠0.5～1.0 mg/kg,大鼠2 mg/kg ip)能明显对抗吗啡镇痛作用;优降宁(小鼠35 mg/kg,大鼠50 mg/kg ip)能明显增强吗啡镇痛作用,并能“逆转”利血平对抗吗啡镇痛作用。其“逆转”作用的强弱取决于利血平、优降宁给药的先后次序。     

EFFECTS OF CLONIDINE ON BLOOD PRESSURE AND HEART RATE RESPONSES TO AN EMOTIONAL STRESS IN THE RAT: A SPECTRAL STUDY

1. The fluctuations that underlie the spontaneous variability of blood pressure (BP) and heart rate (HR) were investigated in conscious normotensive rats using power spectral analysis. 2. Air jet stimulation determined a significant BP rise associated with a tachycardia. This environmental mild stressor amplified the 195-605 mHz oscillations of HR which are under autonomic control. No habituation to this stressor was observed since a second stimulation determined similar responses. 3. Clonidine (10 micrograms/kg, i.v.) prevented the BP rise normally associated with air jet stimulation. In addition, clonidine dramatically reduced the amplitude of BP and HR oscillations in the frequency region of 195-605 mHz. 4. It is concluded that a mild emotional stressor elicits in normotensive rats a rise in BP and HR associated with modified spectral profiles reflecting sympathetic hyperactivity. Clonidine minored the effects of stress on BP and HR variability and also prevented BP elevation.     

EFFECTS OF CA2+ ANTAGONISTS ON CARDIOVASCULAR RESPONSES TO POSTERIOR HYPOTHALAMIC STIMULATION IN THE RAT

The effects of methoxyverapamil or hydralazine on pressor responses to posterior hypothalamic stimulation and injected pressor agents were studied in normotensive male Wistar rats. Methoxyverapamil inhibited both phases of pressor responses to hypothalamic stimulation and pressor responses to injected noradrenaline or angiotensin II. Hydralazine inhibited the secondary phase (due to adrenomedullary catecholamine) and not the primary phase (due to increased sympathetic vasomotor activity) of pressor response to hypothalamic stimulation. However, it inhibited the pressor responses to exogenous noradrenaline or angiotensin II. The data indicate that hydralazine is ineffective in inhibiting the pressor response elicited by noradrenaline endogenously released at the sympathetic nerve endings.     

灵芝多糖对老年小鼠脾细胞DNA多聚酶α活性及免疫功能的影响

24月龄老年小鼠脾细胞中DNA多聚酶α的活性比3月龄小鼠明显低下。每日ip灵芝多糖(GL-B)25和50 mg·kg^-1共4 d,均可明显增强老年小鼠脾细胞内DNA多聚酶α的活性,与老年对照组相比分别增加44.0和58.4%。体外实验发现,老年小鼠脾细胞自发增殖能力和自发分泌IL-2的能力明显低于年轻对照组,对同种异型抗原引起的混合淋巴细胞反应也明显减弱,加入GL-B(50,100,200μg·ml^-1)以后,这些指标均可明显恢复。