小鼠化学性迷路切除后的异食癖行为和前庭功能损害

目的建立一种新的、简便、易操作的评价小鼠前庭功能损害的整体动物模型。方法昆明种小鼠分对照组、旋转组、假损伤组和前庭损伤组4组,每组8只。化学性迷路切除由戊巴比妥钠麻醉下双侧鼓室内注射对氨基苯砷酸(arsanilic acid)0.040ml(100mg/ml)造成,恢复3d转入代谢笼单笼饲养。对照小鼠注射等容生理盐水。小鼠每天被放入直径20cm的水平转台,以70r/min变速旋转75s(转15s停5s),连续3d,以及旋转后5d,检测食量、异食高岭土量、接触翻正反射恢复(CRR)时间和露头游泳时间。结果旋转前的3d,对照组、旋转组、假损伤组与前庭损伤组小鼠的食量和异食高岭土量差异无统计学意义。旋转的3d以及旋转后的5d,假损伤组与前庭损伤组小鼠的平均食量在4.36~4.40g,差异无统计学意义。旋转组2和3d异食高岭土量分别增加185%和223%。假损伤组小鼠旋转的3d,平均异食高岭土量则从旋转前的0.12g分别增加到0.29g,0.36g(P<0.01)和0.35g(P<0.01);旋转后1d下降至0.25g(P<0.01),2d为0.17g,3~5d则与前庭损伤组持平。旋转3d和旋转后5d的前庭损伤组小鼠,平均异食高岭土量始终为0.12~0.15g。假损伤组小鼠平均CRR和露头游泳时间分别为3.13和59.4s,而前庭损伤组小鼠分别为36.3和19.1s。结论双侧化学性迷路切除小鼠对被动运动诱发的3种行为反应消失,可作为一种评价药物对前庭损害的行为模型。     

侧脑室或鞘内注射烟碱对恩氟烷催眠和镇痛作用的影响

目的初步分析恩氟烷的催眠和镇痛作用与神经元烟碱受体之间的关系。方法催醒实验:小鼠ip恩氟烷2.2mL.kg-1,翻正反射消失1min后,分别脑室注射烟碱10,20和40μg(5μL),记录翻正反射恢复时间(即睡眠时间)。镇痛实验:①甲醛实验:小鼠ip恩氟烷0.5mL.kg-1,5min后分别鞘内注射烟碱5,10和15μg(5μL),再5min后于足底皮下注射2%甲醛溶液20μL,记录60min内小鼠舔被注射足的累积时间。②热板实验:给药方法同甲醛实验,于注射烟碱后5,10,15,20和25min记录小鼠足部接触热板至开始添后足的时间作为后足痛阈。结果脑室注射烟碱能明显减少恩氟烷催眠小鼠的睡眠时间;鞘内注射烟碱不能拮抗甲醛实验中恩氟烷的镇痛作用,但可拮抗热板实验中恩氟烷的镇痛作用。结论神经元烟碱受体可能是恩氟烷催眠作用的重要靶位之一;也可能是恩氟烷对热刺激镇痛作用的重要靶位之一,而非对化学、炎性刺激镇痛作用的靶位。     

葛花水提液对小鼠急性酒精性行为障碍的药效观察

目的 观察葛花水提液改善小鼠急性酒精性行为障碍的作用.方法 采用灌服浓度为40%的酒精溶液造成小鼠急性酒精性行为障碍,以转棒实验和翻正反射实验等量化行为学指标为判断依据.结果 葛花水提液高、低剂量组小鼠在转棒上停留时间与模型组比较有显著性差异,翻正反射的耐受时间和维持时间与模型组比较有显著性差异.结论 葛花水提液能改善小鼠急性酒精性行为障碍.     

注射用尼莫地平脂质体对大鼠全脑缺血再灌注和小鼠缺氧性损伤的保护作用

目的：研究注射用尼莫地平脂质体（NDLI）对大鼠全脑缺血再灌注和小鼠缺氧性损伤的保护作用。方法：采用小鼠常压耐缺氧实验和小鼠断头实验，观察NDLI对小鼠耐缺氧能力的影响；采用Pulsinelli四动脉结扎法略加改良制作全脑缺血模型，记录对脑电图（EEG）及翻正反射的恢复时间、脑组织匀浆伊文思蓝含量的影响。结果：NDLI能显著延长小鼠的存活时间及断头后喘气持续时间，缩短大鼠脑电图及翻正反射的恢复时间，降低脑匀浆伊文思蓝的含量。结论：NDLI对全脑缺血再灌注和缺氧性损伤有明显的保护作用。     

解酒饮的药理学研究

目的:研究解酒饮的解酒作用.方法:40只小鼠随机分成空白对照组,胆维他对照组(25mg·g-1)和高低剂量解酒饮组(25,12.5g·kg-1).用自制30%白酒按14mL·kg-1灌胃造成小白鼠醉酒模型,分别在造模前后单次给药,观察小白鼠翻正反射消失的时间和小鼠酒醉持续时间.结果:与空白对照组比较,解酒饮25g·kg-1组小鼠翻正反射消失时间显著延长,酒醉持续时间显著缩短.而解酒饮12.5g·kg-1组无显著性差异.结论:按生药25g·kg-1给予解酒饮,对于小白鼠具有预防醉酒和醒酒的作用.     

醒酒浓缩液的药效学研究

目的观测醒酒浓缩液对醉酒小鼠防醉和解酒作用.方法采用醉酒模型并测试小鼠翻正反射消失时间及恢复时间(min),气相色谱检测血中乙醇含量.结果 (1)30mL/kg、40mL/kg醒酒浓缩液对醉酒小鼠具有明显防醉和解酒作用(P<0.05～0.01);(2)醉酒前给小鼠ig醒酒浓缩液,中、高剂量组能明显降低酒后40～120min内血液中乙醇含量(P<0.05～0.01).结论本品具有较好预防醉酒和解酒作用,其作用机理可能与其降低血中乙醇含量有关.     

四逆散冻干粉中的柴胡皂苷C对小鼠睡眠影响的实验研究

目的研究四逆散冻干粉中主要成分柴胡皂苷C对小鼠睡眠的影响。方法将小鼠随机分成3组:空白对照组、模型组和给药组,四逆散冻干粉中有效成分柴胡皂苷C 12 g.kg-1经灌胃给予给药组;空白对照组、模型组均给予同体积的蒸馏水。于末次给药前8 h禁食,给药60 min后,腹腔注射50 mg.kg-1戊巴比妥钠,观察并记录翻正反射消失至恢复时间,即睡眠时间。结果柴胡皂苷C可明显延长戊巴比妥钠所致小鼠睡眠时间,与空白组比较具有极显著性差异(P<0.01)。结论四逆散冻干粉中有效成分柴胡皂苷C可延长阈剂量戊巴比妥钠所致小鼠睡眠时间,效果明显。     

环孢菌素对麻醉药作用的影响

本文报道小鼠肌注单剂量环孢菌素对戊巴比妥引起的睡眠作用和芬太尼的镇痛作用的影晌.给小鼠肌注环孢菌素60mg/kg,2h后,腹腔注射戊巴比妥钠50mg/kg,测定小鼠翻正反射消失到恢复的时间,测得小鼠睡眠时间为70.4±4.2min(n=6),与给予相同剂量戊巴比妥钠对照组(睡眠时间为30.4±3.2min)相比较,其睡眠时间延长2.3倍.小鼠分组肌注     

护肝颗粒对小鼠急性肝损伤的保护作用

目的:研究护肝颗粒对模型小鼠急性肝损伤的保护作用。方法:以0.12%氯仿-花生油溶液经腹腔注射,制备小鼠肝损伤模型,显微镜下观察肝组织病理学变化;测定丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量;计算肝脏指数。结果:高、中、低剂量护肝颗粒均能显著降低急性肝损伤模型小鼠血清中ALT、AST活性,提高其SOD活性,降低其MDA含量及肝脏指数。结论:护肝颗粒对急性肝损伤有一定的保护作用。     

醒酒浓缩液的药效学研究

目的观测醒酒浓缩液对醉酒小鼠防醉和解酒作用。方法采用醉酒模型并测试小鼠翻正反射消失时间及恢复时间（min），气相色谱检测血中乙醇含量。结果(1)30mL/kg、40mL/kg醒酒浓缩液对醉酒小鼠具有明显防醉和解酒作用（P<0.05～0.01）；（2）醉酒前给小鼠ig醒酒浓缩液，中、高剂量组能明显降低酒后40～120min内血液中乙醇含量（P<0.05～0.01）。结论本品具有较好预防醉酒和解酒作用，其作用机理可能与其降低血中乙醇含量有关。     

The effects of long-term, low-dose diazepam treatment on the guinea pig righting reflex and medial vestibular nucleus neuronal activity

Guinea pigs received a 2 mg/kg IP injection of diazepam, or an equivalent volume of vehicle, daily for 28–60 days. To determine whether tolerance developed to the ataxic effects of diazepam on the righting reflex, daily righting reflex latency (RRL) measurements were made before and 20, 30, and 40 min following the diazepam or vehicle injection for 28 days. Analyses of the RRLs for individual animals indicated that a significant decrease in RRL over time (indicating tolerance) occurred in only one out of nine animals receiving diazepam and in none of the vehicle animals. Medial vestibular nucleus (MVN) neurons in brain stem slices from animals receiving chronic diazepam treatment had a significantly higher average firing rate than those from vehicle controls. These results suggest that: a) long-term treatment with single 2 mg/kg daily IP injections of diazepam does not result in tolerance to diazepam's ataxic effects on the righting reflex in the majority of animals; b) this form of diazepam treatment may, nonetheless, induce a hyperactivity of brain stem MVN neurons that may be consistent with the occurrence of a withdrawal syndrome.     

Protective effect of hydrocortisone on iminodipropionitrile-induced neurotoxicity in rats

Occupational and environmental exposure of synthetic nitriles is of potential relevance to human health. Iminodipropionitrile (IDPN), a prototype nitrile toxin, has been shown to produce dyskinetic syndrome in rodents. This study reports the effect of concomitant exposure of rats to hydrocortisone and IDPN on behavioural abnormalities namely excitation, circling and chorea (ECC) syndrome. Four groups of female Wistar rats were given hydrocortisone (0, 10, 30 and 60 mg/kg, gavage, for 10 days) 30 min. before IDPN (100 mg/kg, intraperitoneally for 8 days). Two additional groups of rats were treated with either saline (control group) or 60 mg/kg of hydrocortisone (drug alone group). The animals were observed for neurobehavioural abnormalities including dyskinetic head movement, circling, tail hanging, air righting reflex and contact inhibition of righting reflex. After behavioural studies, the animals were killed, and the discrete brain regions and temporal bones were collected for biochemistry and inner ear histopathology, respectively. Hydrocortisone significantly and dose dependently attenuated the incidence and severity of IDPN-induced behavioural syndrome. Administration of hydrocortisone (60 mg/kg) alone significantly increased glutathione (GSH) levels in olfactory bulb and striatum, whereas IDPN alone significantly reduced GSH levels in olfactory bulb, striatum and hippocampus. Hydrocortisone (60 mg/kg) significantly compensated IDPN-induced depletions of GSH in different brain regions. Hydrocortisone also protected the animals against IDPN-induced vestibular hair cell degeneration. The protective effect of hydrocortisone may be attributed to its anti-inflammatory and antioxidant properties.     

Nephrotoxic and Ototoxic Effects of Hydroxygentamicin in Cats

Nephrotoxic and Ototoxic Effects of Hydroxygentamicin in Cats.Slighter, R. G, FABIAN, R. J., DONIKIAN, M. R., RENCH, R. D.,NEIDL, M. J., AND BOSHART, C. R. (1984). Fundam. Appl. Toxicoi.4, 568–576. Hydroxygentamicin, an aminoglycoside antibiotic,was administered subcutaneously to cats in doses up to 160 mgbase/kg daily for 10 to 13 weeks. Gentamtcin and a vehide solutionwere tested as positive and negative control, respectively;in one test netilmicin was also included for comparative purposes.Several parameters, including serum urea nitrogen, serum creatinine,organ/body weight ratios, serum and tissue concentrations ofthe antibiotics, and renal pathology, were determined to ascertainthe nephrotoxic potential of the three ami-noglycosides. Inaddition, observations for the onset of ataxia and impairmentof righting reflex were made during the course of the studiesto compare the vestibular ototoxic effects of the three antibiotics.Although serum urea nitrogen and serum creatinine values increasedmarkedly in those cats which eventually died or were sacrificedmoribund, these parameters in survivors were slightly but notsignificantly higher than controls. -Serum concentrations ofthe drugs were proportional to the doses administered, but renalconcentrations were approximately two and five times as highfor netilmicin and gentamicin, respectively, as they were forequivalent doses of hydroxygentamicin. The morphological changesobserved in the kidney of cats given 60 mg base/kg of hydroxygentamicinwere slightly less than those seen in cats administered 10 mgbase/ kg of gentamicin; similarly, kidney changes in cats givennetilmicin were observed approximately twice as frequently asthey were in those receiving equivalent doses of hydroxygentamicin.The nephrotoxic effects of aminoglycoside antibiotics were directlyrelated to renal drug concentration and not to serum concentration,which was a function of dose. The reason for the lower incidenceof vestibular ototoxic effects with hydroxygentamicin than withgentamicin was not as readily apparent. Vestibular damage resultingfrom netilmicin administration was restricted to ataxia; thelack of righting reflex impairment in all five cats was notcharacteristic of the pattern of vestibular ototoxicity associatedwitn aminoglycoside therapy.     

Seasonal and sex influences on ketamine-induced analgesia and catalepsy in the rat; a possible role for melatonin

Data from this laboratory on ketamine-induced analgesia and catalepsy in rats revealed that factors other than dose modified the difference in the latency of the tail flick response (TFLD), a measure of analgesia, and the duration of the loss of the righting reflex (DLRR), a measure of catalepsy. Untreated female rats showed a longer latency than males in their response to a noxious stimulus at midnight, but not at noon. Females also showed a longer loss of righting reflex response to ketamine than did males, whether at noon or midnight; the loss of righting reflex at night was augmented in both. Although females showed analgesia with administration of ketamine at doses smaller than those which induced catatonia, males showed no analgesia without catatonia and comparable loss of the righting reflex occurred at doses much larger than for females. There was a 3-fold increase in the latency of the tail flick response and loss of righting reflex during the winter, as compared with summer, for females treated with ketamine; males showed a similar variation in the loss of righting reflex. Since analgesia is produced by both melatonin and ketamine, and since ketamine appears to share opiate receptors with an endogenous ligand, beta-endorphin, a role was sought for the pineal and melatonin in the variation of responsiveness to ketamine. Pinealectomized rats failed to show augmentation of the loss of righting reflex induced by ketamine at night and mice showed a seasonal variation in the analgesia induced by melatonin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Attenuation of iminodipropionitrile induced behavioral syndrome by sodium salicylate in rats

Iminodipropionitrile (IDPN) produces irreversible behavioral abnormalities characterized by excitation with choreiform and circling movements (ECC) syndrome in rodents. Concomitant exposure to drugs or environmental chemicals has been shown to alter IDPN-induced neurobehavioral toxicity. This investigation was undertaken to study the effect of sodium salicylate (SS) on IDPN-induced behavioral abnormalities in rats. The animals were exposed to IDPN (100 mg/kg ip) daily for 8 days. SS was administered daily 30 min before IDPN in the doses of 50, 100 and 200 mg/kg ip for 12 days. The animals were observed for neurobehavioral abnormalities including dyskinetic head movements, circling, tail hanging, air righting reflex and contact inhibition of the righting reflex. Horizontal and vertical locomotor activities and forelimbs grip strength were also measured. After behavioral studies, the animals were sacrificed, and the cerebrum and temporal bones were collected for glutathione analysis and inner ear histopathology, respectively. The onset of ECC syndrome was observed on Day 9 in the IDPN-alone group with 100% incidence on Day 12. Cotreatment with salicylate dose-dependently delayed the onset time and significantly attenuated the incidence and severity of IDPN-induced neurobehavioral signs. IDPN alone significantly increased horizontal motor activity and reduced vertical motor activity and forelimbs grip strength; these effect were significantly reversed by salicylate treatment. Treatment with salicylate also attenuated IDPN-induced depletion of GSH in the cerebrum, suggesting its free radical scavenging property.     

Effect of the dopamine receptor agonist apomorphine on sensory input

Summary The study examines the hypothesis that changes in behavioural responsiveness induced by apomorphine reflect an effect of the drug on visual, tactile, vestibular, or proprioceptive sensory input. Rats were injected with apomorphine (1.25 mg/kg) and administered a neurological examination in which stimuli from the different sensory modalities were tested for their ability to elicit a limb placing response. Results indicate that these sensory stimuli were equally effective in eliciting reflex placing reactions in saline-and apomorphine-treated rats. Thus, contrary to the hypothesis, apomorphine does not appear to affect the reception of visual, tactile, vestibular, or proprioceptive sensory input. Tests of equilibration (righting) induced by static tilt revealed a fractionated response under apomorphine (0.6–5 mg/kg). Since the response to tilt probably involves striatal integration of vestibular and proprioceptive input, it is suggested that apomorphine disrupts sensory or sensorimotor integration. Send offprint requests to H. Szechtman at the above address     

Pharmacological and Metabolic Interactions between Ethanol and Methyl n-Butyl Ketone, Methyl Isobutyl Ketone, Methyl Ethyl Ketone, or Acetone in Mice

Methyl n-butyl ketone (MnBK), methyl isobutyl ketone (MIBK),methyl ethyl ketone (MEK), and acetone are widely used industrialsolvents to which certain groups of workers are exposed. Pharmacologicaland metabolic interactions between these solvents and ethanolwere explored in male CD-1 mice. The effects of these solventson the duration of ethanol-induced loss of righting reflex andon ethanol elimination in mice were studied. The solvents weredissolved in corn oil and injected intraperitoneally 30 mm beforeethanol 4 g/kg ip. The four solvents prolonged significantlythe duration of ethanol-induced loss of righting reflex whengiven in the following doses (m mol/kg): MnBK, 3.75 and 5; MIBK,5; MEK, 5 and 10, acetone, 20 and 40. This prolongation wasdose related and increased as the dose of the solvent was increased.The concentrations of ethanol in blood or brain on return ofthe righting reflex were similar in solvent-treated and controlanimals, with the exception of the group of mice treated with40 mmol/kg acetone in which the ethanol concentrations weresignificantly lower than in control animals. The mean eliminationrate of ethanol was markedly reduced in mice treated with MnBK5 mmol/kg, MEK 15 mmol/ kg, and acetone 40 mmol/kg. All foursolvents reduced the activity of mouse liver alcohol dehy-drogenasein vitro. It is concluded that enhancement of the ethanol-inducedloss of righting reflex by these solvents in mice is well correlatedto reduced elimination rate of ethanol.     

侧脑室注射蝇蕈醇和荷包牡丹碱对大鼠异氟烷最低麻醉浓度的影响

大鼠侧脑室置管后2 d, 观察icv GABA_A受体激动剂蝇蕈醇和(或)其拮抗剂荷包牡丹碱对麻醉箱内异氟烷最低有效浓度（反映最低肺泡有效浓度）和翻正反射恢复时间的影响. 结果表明icv 5 mmol·L^-1蝇蕈醇2 μL明显降低箱内异氟烷最低麻醉浓度, 延长大鼠翻正反射恢复时间; icv 0.5 mmol·L^-1荷包牡丹碱2 μL对异氟烷的最低麻醉浓度和翻正反射恢复时间皆无影响, 但可部分拮抗蝇蕈醇降低异氟烷最低麻醉浓度和延长翻正反射恢复时间的作用. 以上实验结果提示, 蝇蕈醇和异氟烷间有协同作用, 但脑内的GABAA受体可能不是异氟烷全麻作用的主要靶位.     

小鼠伍用氯胺酮与赛拉嗪翻正反射和毒性的影响

观察了氰胺酮（Ｋｅｔ）与赛拉嗪（Ｘｙ１）以１：１和３：１配伍对小鼠急性毒性和翻正反射消失效应的影响。用Ｑ（ｘ）统计检验合用后的联合作用性质，并绘制出Ｑ曲线及其９５％可信限图．可见Ｋｅｔ与Ｘｙｌ以１：１和３：１伍用后毒性分别为相加和轻微协同，翻正反射消失效应均呈协同性增强．配伍后的治疗指数，安全指数及可靠安全系数都较单药提高．大鼠和大的实验结果也表明Ｋｅｔ与Ｘｙｌ伍用后效应增强．     

Methionine enhances alcohol-induced narcosis in mice.

Methionine is an essential amino acid that has been used as a therapeutic drug in some disorders. In this study we questioned whether methionine affects ethanol-induced loss of righting reflex (narcosis). One hour after IP methionine administration (60, 120, 240, 480, 720, 960, and 1280 mg/kg), mice were injected with ethanol (4.0 g/kg), and the duration of loss of righting reflex was recorded. Methionine, at the higher doses (960 and 1280 mg/ kg), significantly increased this effect on ethanol-treated animals. A time-course study revealed that methionine increased the duration of the loss of righting reflex induced by ethanol until 4 h after being injected. Because methionine did not affect blood ethanol levels, no change in peripheral alcohol can explain the observed effects. This potentiation was not specific for ethanol because methionine increased 3-methyl-1-butanol (0.6 g/kg) and 1-propanol (2.4 g/kg)-induced loss of righting reflex as well. Therefore, the results obtained in this study suggest the need for further investigation into methionine-ethanol interactions prior to the use of methionine as an agent that can be used as an antidepressant and to prevent damage to organic tissue in alcoholism.