Effects of Ethanol on Locomotor Activity in Rats of Different Ages

Abstract: Using male Sprague-Dawley rats of different ages, simple motor activity was measured over three 4 min. runs in a square open field after ethanol (EtOH, 2 g/kg, intraperitoneally) or saline. The different groups consisted of 12 animals whose mean ages was 20, 40 and 60 days. Motor activity and blood ethanol levels were measured at 30, 60 and 120 min. after injection. Blood ethanol levels (measured after each run) decreased from 1st to 3rd run in 20 and 40 day groups and increased from 1st to 2nd run in the 60 day group, before decreasing. Activity data indicated: 1) decrease in motor activity the 3 runs by all saline and the 21 day EtOH groups, 2) initial lower activity induced by EtOH in all age groups, 3) lack of decrease in activity over 3 runs in 40 and 60 day EtOH groups. All saline and EtOH age groups showed within-run decrease of activity     

Nicotine-induced Perturbations on Heart Rate,Body Temperature and Locomotor Activity Daily Rhythms in Rats

The aim of this study was to evaluate the influence of nicotine on the daily rhythms of heart rate, body temperature and locomotor activity in unrestrained rats by use of implanted radiotelemetry transmitters. The study was divided into three seven-day periods: a control period, a treatment period and a recovery period. The control period was used for baseline measurement of heart rate, body temperature and locomotor activity. During the treatment period three rats received nicotine (1 mgkg^?1, s.c.) at 0900 h. Three rats received saline under the same experimental conditions. Heart rate, body temperature and locomotor activity were continuously monitored and plotted every 10min. During the three periods a power spectrum analysis was used to determine the dominant period of rhythmicity. If daily rhythms of heart rate, body temperature and locomotor activity were detected, the characteristics of these rhythms, i.e. the mesors, amplitudes and acrophases, were determined by cosinor analysis, expressed as means ± s.e.m. and compared by analysis of variance. Nicotine did not suppress daily rhythmicity but induced decreases of amplitudes and phase-advances of acrophases for heart rate, body temperature and locomotor activity. These perturbations might result from the effects of nicotine on the suprachiasmatic nucleus, the hypothalamic clock that co-ordinates biological rhythms.     

Pharmacodynamic Modeling for Change of Locomotor Activity by Methylphenidate in Rats

Purpose. The locomotive activity changes after intravenous (i.v.) administration of methylphenidate (MPD) in rats were pharmacodynamically analyzed. Methods. MPD concentration in plasma, MPD concentration and dopamine (DA) level in striatal dialysate collected by microdialysis method, and the locomotor activity after i.v. administration of MPD (2, 5 and 10 mg/kg doses) were used for the analysis. Results. The transport of MPD from plasma to the interstitial fluid in the brain could be expressed by the linear two-compartment model. The clockwise hysteresis between the MPD concentration and the DA level in the dialysate could be explained by the pharmacodynamic model considering Michaelis-Menten type reuptake process of the extracellular DA into the terminal of the dopaminergic nerve and its competitive inhibition by the extracellular MPD. The inhibition constant (K_i) of MPD for DA reuptake was estimated to be 41.3 ± 73.8 nM (mean ± SE), which was closely consistent with the in vitro value after correction with dialysis recovery. The relationship between DA level in dialysate and locomotor activity was expressed by the Emax model considering two contrary effects, hyperkinesia and stereotypy. The bi-phasic locomotor activity-time profiles after high dose of MPD could be represented by this model. Conclusions. The developed model made it possible to explain the tolerance in DA increase and the complicated locomotive change induced by MPD, and may be useful for other DA reuptake inhibitors, such as amphetamine and methamphetamine.     

Effects of Toluene Inhalation on Carbon Dioxide Production and Locomotor Activity in Mice

Effects of Toluene Inhalation on Carbon Dioxide Production andLocoraotor Activity in Mice. BUSHNELL, P. J., EVANS, H. L.,AND PALMES, E. D. (1985). Fundam. Appl. Toxicol.. 5,971-977.Rapid and noninvasive tests of locomotor activity (LA) and carbondioxide production (minute volume expired CO₂, or _ECO₂)in mice were sensitive to the effects of inhaled toluene. Comparedto sham exposures, toluene at 100 ppm had no effect on LA or_ECO₂; at 1000 and 3000 ppm, LA increasedduring exposure, while _ECO₂ was suppressedfor 6 to 24 min at the beginning of exposure. In a nominal 10,000-ppmexposure, toluene levels were increased from 1000 to 10,500ppm in 60 min. At these levels, toluene abolished LA at concentrationsabove 8000 ppm, and suppressed _ECO₂ throughoutexposure. During recovery from toluene-induced narcosis, bothLA and _ECO₂ were elevated above control.In other studies, groups of mice inhaled toluene daily at 0,100, 1000, or 3000 ppm, 5 hr/day for 8 or 90 days, and weretested individually 30 to 90 min after termination of exposure.Under these conditions, toluene decreased postexposure _ECO₂ for 1–2 weeks, altered the weekly patternof change in _ECO₂, and did not affect LA.No effects of repeated, daily exposure to toluene were observedon body weight. These results demonstrate the utility of thepresent method to detect changes in LA and metabolic rate resultingfrom toluene inhalation, and suggest that different mechanismsare involved in the behavioral and metabolic responses to tolueneinhalation.     

Pretreatment of Rats with an Organophosphorus Insecticide, Chlorfenvinphos, Protects against Subsequent Challenge with the Same Compound1

Pretreatment of Rats with an Organophosphorus Insecticide, Chlorfenvinphos,Protects against Subsequent Challenge with the Same Compound.IKEDA, T., KOJIMA, T., YOSHIDA, M., TAKAHASHI, H., TSUDA, S.,AND SHIRASU, Y. (1990). Fundam. Appl. Toxicol. 14, 560–567.A single oral pretreatment of rats with chlorfenvinphos (CVP)reduced toxicity of the same compound subsequently administered.This protection occurred 8 hr and became maximal 24 hr afterthe oral pretreatment at a dose of 15 mg/kg (about half of itsLD50). The 24-hr pretreatment with CVP increased the LD50 ofCVP threefold, but did not change the type of toxic signs andtime to death caused by CVP. The CVP pretreatment did not appreciablychange the toxicities of the cholinergic agonists, carbacholand oxotremorine, but significantly increased the toxicity ofanother organophosphate, dichlorvos. Oral treatment of ratswith CVP (15 mg/ kg) inhibited brain acetylcholinesterase (AChE)activity. This inhibition became maximal at 4 hr (about 20%of control) and lasted more than 24 hr after the administration.Twenty-four hours after oral administration of CVP (15 mg/kg),the second dose (CVP 30 mg/kg, po) was less effective in inhibitingcholinesterase activities of the brain, erythrocyte, and plasmacompared with naive rats treated with the same dose. The differencein brain AChE activity between control and CVP pretreatmentgroups was greater in magnitude than that measured in erythro-cytes.CVP concentration in plasma after the oral administration ofCVP (30 mg/kg) was decreased by the CVP pretreatment. Area underthe concentration vs time curve (AUC) in the CVP-pretreatedgroup was about one-fourth of AUC in the control group. Thisdecrease in the AUC was comparable to the decrease in the toxicityof CVP. Thus, the protection against subsequent CVP challengemay be due to the reduction in the inhibition of brain AChEactivity caused by the decrease in plasma CVP concentration.     

Effects of Acute and Repeated Exposures to Aroclor 1254 in Adult Rats: Motor Activity and Flavor Aversion Conditioning

While considerable research has focused on the neurotoxicityof developmental exposures to polychlorinated biphenyls, includingAroclor 1254, relatively little is known about exposures inadult animals. This study investigated the behavioral effectsof acute and repeated Aroclor 1254 exposures to adult rats onmotor activity and flavor aversion conditioning. Male Long-Evansrats (60 days old) were tested for motor activity in a photocelldevice after acute (0, 100, 300, or 1000 mg/kg, po) or repeated(0, 1, 3, 10, 30 or 100 mg/kg/day, po, 5 days/week for 4 to6 weeks) exposure to Aroclor 1254. Motor activity was decreaseddose-dependently at doses of 300 mg/kg or more after acute exposure.Severe body weight loss and deaths occurred at 1000 mg/kg. Recoveryof activity occurred over 9 weeks but was incomplete. Afterrepeated exposure, motor activity was decreased dose-dependentlyat doses of 30 mg/kg or more, and severe weight loss and deathsoccurred at 100 mg/kg. In contrast to acute exposure, completerecovery of activity occurred 3 weeks after exposure. Additionalrats were water deprived (30 mm/day) and received acute po administrationof Aroclor 1254 (0, 10, 15, 25, 30, 100, or 300 mg/kg) shortlyafter consuming a saccharin solution. Three days later theywere given the choice between consuming saccharin or water,and saccharin preferences were recorded. Saccharin preferencewas decreased at doses of 25 mg/kg or more. Additional experimentsdetermined the effect of repeated saccharin-Aroclor 1254 pairings(0, 3.75, 7.5, or 15 mg/kg/day, 14 days) followed by a choicetest 1 day after the last dose. Repeated exposure to 15 mg/kgproduced robust flavor aversion conditioning. Repeated exposureto 7.5 mg/kg produced flavor aversion conditioning in four of12 rats. These results demonstrate that Aroclor 1254 causeshypoactivlty and flavor aversions in adult rats; the no observableeffect level (NOEL) for motor activity was 100 mg/kg for acuteexposure and 10 mg/kg for repeated exposure for a period ofup to 6 weeks. The acute NOEL for flavor aversion conditioningwas 15 mg/kg while the repeated NOEL was 7.5 mg/kg.     

复方五味子对应激大鼠垂体-性腺轴及运动能力的影响

［摘要］目的探讨复方五味子对实验性水上漂浮及高强度运动雄性大鼠垂体 性腺轴功能及运动能力的影响。方法选取大鼠58只,分为安静对照组（A组10只）、水上漂浮并高强度运动组（B组12只）、水上漂浮并运动力竭组（C组13只）、水上漂浮并高强度运动+复方五味子组（D组9只）和水上漂浮并运动力竭+复方五味子组（E组14只）。B、C、D和E组参照Bedford的训练模式进行为期10 d的训练,第11天时4组同时进行水上漂浮3 h后,B、D组再行跑台高强度运动3 h,实验结束后测定血清皮质酮（CORT）、睾酮（Tes）、促黄体激素（LH）水平,同时取垂体、一侧睾丸在电子显微镜下观察超微结构;C、E组则进行一次力竭性运动,记录力竭时间。结果①复方五味子能显著提高大鼠力竭时间,力竭延缓率高达63.46%。②B组的Tes水平与A组相比显著降低,而CORT无明显变化。③与A组比较,B组垂体细胞质中分泌颗粒显著减少,D组细胞质中分泌颗粒的数目明显增多。B组睾丸Leydig细胞线粒体肿胀,电子密度增高,嵴减少或消失,D组睾丸Leydig细胞中线粒体结构趋于正常,嵴大多数清晰,可见大小不等深染的分泌颗粒。结论复方五味子有明显的抗疲劳作用,并能保护应激大鼠垂体及睾丸的超微结构,增强大鼠的抗应激能力。     

复方苦参汤对溃疡性结肠炎模型大鼠的干预及作用机制研究

摘 要 目的：探讨复方苦参汤对溃疡性结肠炎（UC）大鼠的作用及机制。方法: 采用2,4,6 三硝基苯磺酸（TNBS）诱导溃疡性结肠炎大鼠模型,用不同剂量的复方苦参汤进行干预,检测结肠组织丙二醛（MDA）、一氧化氮合酶（iNOS）和一氧化氮（NO）水平,以及髓过氧化物酶（MPO）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH Px）活性,观察UC大鼠一般情况和结肠组织形态变化。结果: UC大鼠结肠组织MDA（P＜0.05）、iNOS（P＜0.01）和NO（P＜0.01）水平及MPO（P＜0.01）活性显著高于正常对照组,SOD（P＜0.01）和GSH Px（P＜0.05）活性显著低于正常对照组;复方苦参汤高剂量组治疗后可明显降低UC大鼠结肠组织中MPO（P＜0.01）、MDA（P＜0.05）、iNOS（P＜0.05）和NO（P＜0.01）水平,增加SOD（P＜0.01）和GSH Px（P＜0.05）活性,其疗效呈剂量依赖性。同时大鼠的一般情况及结肠组织形态亦得到明显改善。结论:复方苦参汤能显著抑制UC大鼠氧化应激反应,减轻结肠炎症损伤,具有较高的临床治疗价值。     

亚慢性铅接触大鼠体内钙调素和腺嘌呤核苷三磷酸酶的影响

大鼠以1.318、5.272和10.545mmol醋酸铅染毒3个月。各染毒组大鼠全血中钙调素(CaM)含量和红细胞膜钙-腺嘌呤核苷三磷酸酶(Ca~(2+)-ATPase)活力显著下降,呈剂量-效应关系。高剂量组红细胞钠-钾-腺嘌呤核苷三磷酸酶(Na~+-K~+-ATPase)活力明显抑制。电镜细胞化学观察,肝细胞腺嘌呤核苷三磷酸酶电子密度变浅、分布减少。     

邻苯二甲酸二丁酯对大鼠精子顶体酶活性的影响

目的：观察邻苯二甲酸二丁酯对大鼠精子顶体酶活性的影响。方法：选取SD大鼠150只,随机分为3个周期进行灌胃给药即30 d、60 d、90 d,每个给药周期又分为5个实验组,每组10只动物,即空白对照组、溶剂对照组、邻苯二甲酸二丁酯高中低3个剂量组（1000、200、50 mg·kgbw-1）。灌胃30 d、60 d、90 d后分别测定大鼠精子中顶体酶的浓度。结果：给药60 d、90 d时,邻苯二甲酸二丁酯的中、高剂量组大鼠精子顶体酶的浓度与溶剂对照组比较明显降低;邻苯二甲酸二丁酯的中、高剂量组60 d、90 d大鼠精子顶体酶的浓度与30 d比较明显降低。结论：邻苯二甲酸二丁酯对大鼠精子顶体酶的活性具有明显的抑制作用。     

复方敏宁擦剂对大鼠肠系膜微循环及小鼠毛细血管通透性的影响

目的：研究复方敏宁擦剂对大鼠肠系膜微循环及小鼠毛细血管通透性增高的影响。方法：观察给药前后大鼠腹腔肠系膜毛细血管血流速度、毛细血管口径、毛细血管数量和毛细血管交叉点数等指标的变化，阐明复方敏宁擦剂改善微循环的作用；检测腹腔及皮肤染料渗出的吸光度，观察对小鼠毛细血管通透性增高的影响。结果：复方敏宁擦剂具有一定程度的改善微循环的作用，与基质对照组比较有统计学差异，但没有酚妥拉明组显著（P〈0．01）；对醋酸所致小鼠腹腔毛细血管通透性增高的抑制作用与对照组比较无统计学差异；中、高剂量对二甲苯致小鼠皮肤毛细血管通透性的增高有明显抑制作用（P〈0．01）。结论：复方敏宁擦剂具有改善局部微循环，增加局部营养，并有一定的抗渗出、抗炎的药理作用，值得临床推广使用。     

Effects of Cucurbitacin E,a Tetracyclic Triterpene Compound from Cucurbitaceae,on the Pharmacokinetics and Pharmacodynamics of Warfarin in Rats

This study firstly investigated the effects of cucurbitacin E (CuE), a tetracyclic triterpene compound from Cucurbitaceae, on the pharmacokinetics (PK) and pharmacodynamics (PD) of warfarin, a model CYP2C probe substrate, in the rat. In PK studies, the concentration of warfarin in blood samples was determined by HPLC‐DAD, and the PK parameters were analysed using non‐compartmental methods. In PD studies, the prothrombin time (PT) in blood plasma at each sample point was measured via thromboplastin reagents. CuE treatment (50, 100 and 200 μg/kg, i.p.) decreased warfarin clearance (28–32%), increased the area under the curve (AUC_0–∞; 55–62%) and prolonged plasma half‐life (t_1/2; 58–72%). At the same time, the anticoagulation effect of warfarin (PT_max) was also significantly increased in the presence of CuE. These data demonstrated that CuE affected the PK and PD of warfarin, and these effects may be due to the inhibition of CYP2C activity by CuE. Hence, careful monitoring should be carried out during concomitant use of herbal products containing CuE with drugs that are metabolized by CYP2C enzymes.     

Differential Effects of Morphine-6-glucuronide,an Active Metabolite of Morphine,and Morphine on Locomotor Activity in Mice: Involvement of the Opioid Receptor

Abstract: Subcutaneous administration of morphine (2.5 to 20 mg/kg) or an active metabolite of morphine, morphine-6-glucuronide (2.5 to 20 mg/kg), increased the locomotor activity of mice in a dose-dependent manner. Fifteen mg/kg of morphine and 20 mg/kg of morphine-6-glucuronide were almost equipotent. Subcutaneous administration of the universal opioid antagonist, naloxone, but not the δ-selective antagonist, naltrindole, significantly suppressed the hyperlocomotion induced by morphine (15 mg/kg). On the other hand the subcutaneous administration of relatively higher doses of naloxone or naltrindole significantly reduced the hyperlocomotion induced by morphine-6-glucuronide (20 mg/kg). These findings suggest that agonistic actions at the opioid receptors, especially at the δ- and μ-receptors, contribute to the morphine-6-glucuronide-induced hyperlocomotion.     

复方熊去氧胆酸口服液对大鼠肝纤维化的防治作用

目的：观察复方熊去氧胆酸口服液（C-UDCA）对四氯化碳（CCl4）致大鼠肝纤维化的防治作用。方法：采用皮下注射40%CCl4-花生油溶液制备肝纤维化模型,检测经口给予C-UDCA后对大鼠肝功能指标、肝纤维化各项生化指标及肝组织病理形态学的影响。结果：C-UDCA各剂量组能显著减轻CCl4导致的肝脂肪变性、肝细胞损伤和纤维组织增生。与UDCA相比,C-UDCA-H能显著降低血清ALT、AST、HA、PCⅢ、CⅣ、LN及肝组织Hyp含量,显著升高血清Alb、A/G、肝组织GSH含量;C-UDCA-M亦能显著降低血清HA、LN 含量。结论：C-UDCA对CCl4致大鼠肝纤维化具有一定的防治作用,且C-UDCA-H、C-UDCA-M的作用优于UDCA。     

复方鳖甲软肝片对高脂性大鼠肝脏脂肪变性的影响

目的:观察复方鳖甲软肝片对高脂性大鼠肝脏脂肪变性的影响.方法:采用随机抽样的方法,从50只大鼠中抽取10只为正常对照组,给予普通饲料喂养,其余40只给予高脂饲料喂养,15 d后分为模型对照组和复方鳖甲软肝片低、中、高剂量组.根据肝小叶内含脂滴细胞数与总细胞数的比值,将肝细胞脂肪变性程度进行分级,采用秩和检验的方法,进行等级资料数据的处理.结果:复方鳖甲软肝片低、中、高剂量均有明显减少肝细胞内脂滴的作用.结论:复方鳖甲软肝片对高脂性大鼠肝脏脂肪变性有明显的治疗作用.     

复方银参颗粒对大鼠脑缺血损伤的保护作用

目的 :研究复方银参颗粒 (FYSG)对大鼠缺血性脑损伤的药理作用。方法 :采用Tamura法建立大鼠大脑中动脉阻断模型 ,观察大鼠脑梗塞面积、卒中行为评级 ,测定脑组织水含量、脑指数。结果 :FYSG (10 0g/kg、5 0g/kg)能明显缩小大脑中动脉阻断大鼠脑梗塞面积 ,改善卒中大鼠神经症状 ,降低脑组织含水量、脑指数。结论 :FYSG对大鼠缺血性脑组织损伤具有保护作用。     

复方苦豆子颗粒对高脂血症大鼠血脂代谢的影响

目的:观察复方苦豆子颗粒对高脂血症大鼠血脂代谢的影响。方法:除空白对照组外,用喂饲高脂饲料法复制大鼠高脂模型,实验分空白对照组、高脂模型组、复方苦豆子颗粒组(低、中、高剂量组,分别喂饲生药7g.kg-1.d-1、15g.kg-1.d-1、22g.kg-1.d-1)、血脂康组(0.8g.kg-1.d-1),给药后每4wk抽1次血,连续3次,分别测定血浆总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、极低密度脂蛋白胆固醇(VLDL-C)、高密度脂蛋白胆固醇(HDL-C)、丙二醛(MDA)含量变化。结果:高脂模型组血浆TC、TG、LDL-C、VLDL-C、HDL-C和MDA含量显著上升,同时动脉粥样硬化指数(AI)增加;给予复方苦豆子颗粒4wk后,各组血浆TC、TG、LDL-C、VLDL-C、MDA及AI水平均降低,且呈剂量依赖性。结论:复方苦豆子颗粒对高脂血症大鼠具有调血脂作用。     

Effects of 3-<i>O</i>-Methyldopa, <small>L</small>-3,4-Dihydroxyphenylalanine Metabolite, on Locomotor Activity and Dopamine Turnover in Rats

It has been well known that 3-O-methyldopa (3-OMD) is a metabolite of L-3,4-dihydroxyphenylalanine (L-DOPA) formed by catechol O-methyltransferase (COMT), and 3-OMD blood level often reaches higher than physiological level in Parkinson's disease (PD) patients receiving long term L-DOPA therapy. However, the physiological role of 3-OMD has not been well understood. Therefore, in order to clarify the effects of 3-OMD on physiological function, we examined the behavioral alteration in rats based on locomotor activity, and measured dopamine (DA) and its metabolites levels in rats at the same time after 3-OMD subchronic administration. The study results showed that repeated administrations of 3-OMD increased its blood and the striatum tissue levels in those rats, and decreased locomotor activity in a dose dependent manner. Although 3-OMD subchronic administration showed no significant change in DA level in the striatum, DA metabolite levels, such as 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), and homovanillic acid (HVA) were significantly decreased. After 3-OMD washout period (7?d), locomotor activity and DA turnover in those rats returned to normal levels. Furthermore, locomotor activity and DA turnover decreased by 3-OMD administration were recovered to normal level by acute L-DOPA administration. These results suggested that 3-OMD affect to locomotor activity via DA neuron system. In conclusion, 3-OMD itself may have a disadvantage in PD patients receiving L-DOPA therapy.     

复方红景天提取物对大、小鼠脑缺血模型的保护作用

目的 研究复方红景天提取物对小鼠急性脑缺血和大鼠局灶性脑缺血模型的保护作用。方法 昆明小鼠随机分为假手术组、模型组、尼莫地平阳性对照组及复方红景天提取物高、中、低剂量组（2.18,1.09,0.55 g·kg^-1）,灌胃给药7 d后结扎小鼠双侧颈总动脉合并迷走神经制备小鼠急性脑缺血模型,观察小鼠存活时间。SD大鼠随机分为假手术组、模型组、尼莫地平阳性对照组及复方红景天提取物高、中、低剂量组（1.45,0.73,0.36 g·kg^-1）,线栓法制备大鼠大脑中动脉阻塞模型,复制模型前7 d开始灌胃给药,连续给药10 d。测定大鼠神经行为学及脑梗死比例,原位末端标记法检测神经细胞凋亡率,Western bolt检测caspase-3的表达水平。结果 复方红景天提取物高、中剂量组可延长小鼠存活时间,与模型组相比具有显著性差异（P<0.01或P<0.05）。与模型组相比,复方红景天提取物高、中剂量组能显著降低大鼠神经功能评分（P<0.01或P<0.05）,复方红景天提取物各剂量组均能显著降低大鼠脑梗死比例并抑制皮质区神经细胞凋亡,下调caspase-3的表达（P<0.01或P<0.05）。结论 复方红景天提取物对大、小鼠脑缺血模型均具有保护作用,可明显延长急性脑缺血小鼠的存活时间,减轻局灶性脑缺血大鼠的神经功能损伤,缩小梗死灶,抑制神经细胞凋亡,其机制与下调caspase-3的表达有关。