异丙嗪对异氟烷小鼠镇痛、催眠、遗忘作用和治疗指数的影响

目的观察异丙嗪对异氟烷镇痛、催眠、遗忘作用和治疗指数的影响。方法用热板法和扭体法观察异丙嗪对异氟烷镇痛作用的影响,翻正反射法观察异丙嗪对异氟烷小鼠睡眠时间的影响,Morris水迷宫法观察异丙嗪对异氟烷小鼠遗忘作用的影响,并用序贯法观察异丙嗪对异氟烷小鼠催眠ED50、LD50的影响。结果在热板法和扭体法实验中,异丙嗪增强了异氟烷的镇痛作用(P<0.05或P<0.01);在翻正反射实验中,异丙嗪可延长异氟烷小鼠的睡眠时间(P<0.01);在水迷宫实验中,异丙嗪组和异氟烷组的平均逃避潜伏期均少于两药合用组(P<0.05或P<0.01),第3象限停留时间均多于两药合用组(P<0.01或P<0.05),异氟烷组原平台穿越次数多于合用组(P<0.05);异丙嗪可降低异氟烷小鼠的催眠ED50(P<0.01),而对其LD50无影响(P>0.05)。结论异丙嗪可以增强异氟烷的镇痛、催眠和遗忘作用,并可以提高异氟烷的治疗指数。     

鞘内注射p-MPPF对异氟烷镇痛作用的影响

目的探讨异氟烷(isoflurane,Iso)镇痛作用与小鼠脊髓5-HT1A受体的关系。方法昆明种小鼠腹腔注射Iso建立镇痛模型。分别以甩尾法、热板法、醋酸扭体法(15min内)评估小鼠鞘内注射5-HT1A受体拮抗剂p-MPPF(6μg和3μg)对Iso镇痛作用的影响。结果单独鞘内注射p-MPPF对小鼠甩尾潜伏期、热板痛阈、扭体次数无影响(P>0.05)。与Iso镇痛组(Iso组)相比,合用药组(Iso+M6组,Iso+M3组)甩尾潜伏期与热板痛阈均缩短(P<0.01或P<0.05);Iso+M6组扭体次数较Iso组增多(P<0.05),Iso+M3组无变化(P>0.05)。结论 Iso体表镇痛作用与激动小鼠脊髓5-HT1A受体密切相关。     

咪达唑仑和芬太尼的相互作用

目的:观察芬太尼与咪达唑仑合用对小鼠学习记忆和镇痛、催眠作用的影响.方法:将小鼠分为:咪达唑仑组(M)、芬太尼组(F)和咪达唑仑+芬太尼组(MF).用避暗实验观察3组的学习记忆的功能;用甩尾实验和扭体实验观察3组的镇痛作用;用翻正反射实验观察3组的催眠作用.结果:与M组、F组相比,MF组进入暗室的潜伏期和错误次数均相似(P>0.05);MF组痛阈明显升高、扭体次数明显减少(P<0.01);MF组的翻正反射持续时间延长.结论:咪达唑仑和芬太尼两药合用镇痛作用与催眠作用增强,但学习记忆无明显改变.     

咪达唑仑对七氟烷镇痛和催眠作用的影响

目的观察咪达唑仑对七氟烷镇痛和催眠作用的影响。方法将40只小鼠随机均分成四组:生理盐水(NS)组、咪唑安定+NS组(M组)、NS+七氟烷组(S组)和咪达唑仑+七氟烷组(MS组)。实验方法:咪达唑仑2.7 mg/kg腹腔注射;甩尾法、催眠实验中分别腹腔注射七氟烷2.1、3.8 ml/kg;扭体法实验中皮下注射七氟烷3.0 ml/kg。甩尾法记录小鼠尾巴自进入水中到甩出水面的时间(甩尾潜伏期,TFL);扭体法观察小鼠腹腔注射1%冰醋酸0.1 ml/10 g后,15 min内的扭体次数;催眠实验记录小鼠翻正反射消失至恢复的时间(睡眠时间)。结果与NS组比较,S组、MS组TFL和睡眠时间延长,扭体次数减少(P<0.05);与S组比较,MS组TFL和睡眠时间明显延长,扭体次数减少(P<0.05)。结论咪达唑仑可增强七氟烷的镇痛及催眠效应。     

异氟烷催眠、镇痛作用与NMDA受体甘氨酸位点的关系

目的分析异氟烷催眠、镇痛作用与NMDA受体甘氨酸位点的关系。方法建立小鼠异氟烷注射催眠、镇痛模型后,在小鼠催醒、甩尾、福尔马林实验中,观察侧脑室或鞘内注射NMDA受体甘氨酸位点的激动剂D-丝氨酸(D-Serine,D-Ser)后小鼠睡眠时间、甩尾潜伏期或累计舔足时间的变化;用免疫组化方法观察异氟烷及鞘内用药对福尔马林小鼠脊髓Fos蛋白表达的影响。结果侧脑室注射D-Ser对异氟烷的催眠时间无影响(P>0.05)。鞘内注射D-Ser(0.025、0.05、0.1ng)可拮抗甩尾实验、福尔马林实验Ⅰ相中异氟烷的镇痛作用(P<0.05,P<0.01),而对福尔马林实验Ⅱ相异氟烷的镇痛作用无影响(P>0.05)。鞘内注射D-Ser0.05ng可拮抗异氟烷对福尔马林小鼠脊髓Fos蛋白表达的抑制作用(P<0.01)。结论异氟烷催眠作用与脑内NMDA受体甘氨酸位点关系不大;脊髓NMDA受体甘氨酸位点介导异氟烷对热、化学刺激的镇痛作用,而与异氟烷对慢性炎性疼痛的镇痛作用无明显关系。     

催眠方煎剂的镇静催眠作用研究

目的:研究中药复方催眠方的镇静、催眠作用。方法:实验分为空白对照(等容生理盐水)、地西泮(0.002g/kg)与催眠方煎剂高、中、低剂量(4、2、1g/kg)组。通过小鼠自主活动实验观察其对小鼠活动的影响,通过阈上和阈下剂量戊巴比妥钠的睡眠实验观察其对小鼠入睡潜伏期和睡眠时间的协同影响作用。结果:与空白对照组比较,催眠方煎剂高、中、低剂量组小鼠自主活动次数显著减少;睡眠潜伏时间显著缩短,睡眠时间显著延长(P<0.01或P<0.05)。结论:催眠方煎剂具有一定的镇静、催眠作用。     

加巴喷丁对小鼠镇痛、镇静及学习记忆的影响

目的观察加巴喷丁(GBP)灌胃对小鼠镇痛、自主活动和学习记忆的影响。方法按分层随机区组设计,将200小鼠分为甩尾法、扭体法、镇静实验、避暗法和跳台法实验组,每实验组40只小鼠,再分为4小组(n=10):生理盐水组(NS组),3个剂量(50,100,200 mg·kg-1)GBP组即GBP50、GBP100、GBP200组。给药一次后,测试小鼠甩尾潜伏期、15 min内扭体次数、5 min内自主活动次数、避暗潜伏期及错误次数、跳台潜伏期及错误次数。结果在甩尾法和扭体法实验中,GBP可产生镇痛作用(P<0.05或P<0.01);自主活动实验中,G100、G200组小鼠表现有镇静作用(P<0.01);在避暗实验和跳台实验中,G100、G200组的潜伏期缩短,错误次数增加(P<0.05)。结论加巴喷丁灌胃产生了镇痛、镇静和遗忘作用。     

孟鲁司特对氯胺酮镇痛效应的影响

目的观察白三烯受体拮抗剂孟鲁司特对静脉麻醉药氯胺酮镇痛效应的影响。方法取40只小鼠,♀♂各半,随机分为4组:生理盐水对照组(NS)、氯胺酮处理组(K)、孟鲁司特处理组(M)、孟鲁司特和氯胺酮联合用药组(M+K)。通过醋酸致小鼠扭体法观察小鼠给药后扭体潜伏期和次数的变化。另取40只小鼠,♀♂各半,随机分为上述4组,利用甩尾实验分别观察给药后小鼠对热水和冰水痛阈值的改变。第3批实验再取40只♀♂小鼠,随机分为上述4组,采用热板法检测给药后小鼠痛阈值的变化。结果孟鲁司特单独用药对小鼠扭体潜伏期和次数、热水和冰水甩尾痛阈值、以及热板痛阈值均无明显影响;氯胺酮能够延长醋酸致小鼠扭体的潜伏期,并且减少醋酸致小鼠扭体的次数,升高小鼠对热水、冰水甩尾和热板痛阈值;而孟鲁司特能够进一步增强氯胺酮的这些效应。结论孟鲁司特能够明显增强氯胺酮对小鼠的镇痛效应。     

恩氟烷镇痛作用与脊髓5-HT1A受体的关系

目的探讨恩氟烷镇痛作用与脊髓5-羟色胺受体1A(5-HT1AR)之间的关系。方法腹腔注射恩氟烷建立镇痛模型,用甩尾法、热板法和扭体法分别观察鞘内注射5-HT1AR特异性拮抗剂p-MPPF对小鼠甩尾潜伏期(TFL)、热板法痛阈(HPPT)和扭体次数(WTs)的影响。结果腹腔注射恩氟烷可产生镇痛作用(P<0.05);单用p-MPPF 4μg/只或8μg/只对小鼠TFL、HPPT和WTs均无明显影响(P>0.05);两个剂量的p-MPPF均能使恩氟烷镇痛小鼠的TFL、HPPT缩短和WTs增加(P<0.05)。结论恩氟烷镇痛作用与脊髓5-HT1AR密切相关。     

氟哌啶醇对曲马多镇痛作用的影响

目的观察氟哌啶醇（haloperidol,HA）对曲马多（TRamadol,TR）镇痛效应的影响,为临床联合用药提供实验依据。方法小鼠分生理盐水NS组,单用TR、HA,HA与TR合用组,用甩尾法和扭体法实验,观察HA对TR镇痛小鼠甩尾潜伏期（tail flick latency,TFL）和扭体次数的影响。结果氟哌啶醇单独用药能提高小鼠对热刺激致痛的痛阈（P〈0．05）,显著减少醋酸致小鼠扭体反应次数（P〈0．01）,氟哌啶醇与曲马多联合应用较两药单用,小鼠的痛阈提高（P〈0．05）、扭体次数明显减少（P〈0．01）。结论氟哌啶醇有镇痛作用,与曲马多合用,镇痛作用增强。     

Influence of opioid receptor antagonists on motor-impairing effects of benzodiazepines

The influence of naloxone and naltrexone on the motor-impairing effects of diazepam, chlordiazepoxide, clonazepam and estazolam were studied in the aerial righting reflex test (mice, rats), and the first two drugs were examined in the rota-rod test (mice). Benzodiazepine-induced motor incoordination was significantly decreased by naloxone and naltrexone (4-16 mg/kg) in mice and rats in aerial righting reflex test. The motor-impairing effects of diazepam and chlordiazepoxide observed in rota-rod test were significantly diminished only by naltrexone (8-16 mg/kg). These data seem to confirm some interactions between benzodiazepines and opioid system.     

Involvement of a GABAergic mechanism in the anticonvulsant effect of pentobarbital against maximal electroshock-induced seizures in rats

The interaction between pentobarbital and other modulators of GABAergic transmission (diazepam, ethanol and progabide) was investigated on maximal electroshock seizures and on the loss of righting reflexes in rats. Pentobarbital, diazepam and ethanol produced a dose-dependent protection against electroshock seizures, with pentobarbital being more potent (3- and 50-times) than diazepam and ethanol. Progabide neither provided protection nor caused loss of righting reflex. Subprotective doses of pentobarbital and diazepam, together or when combined with a single ineffective dose of ethanol or progabide, caused protection against seizures and loss of righting reflex for variable durations, while ethanol and progabide combination did not provide protection. The protective effect of diazepam was antagonized by RO15-1788, picrotoxin and bicuculline pretreatments. The antagonism of pentobarbital protection by a specific GABA receptor antagonist, bicuculline suggests involvement of the GABAergic system in the anticonvulsant effect of pentobarbital. These results indicate that, like diazepam, the anticonvulsant effect of pentobarbital appears to be mediated through a GABAergic mechanism.     

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.     

Interaction of Sambucus nigra Flower and Berry Decoctions with the Actions of Centrally Acting Drugs in Rats

The effect of flower and berry decoctions of Sambucus nigra on the hypnotic action of phenobarbitone (30 mg/ml) and the analgesic action of morphine (5 mg/ml) in rats is described. Wistar laboratory rats received 2 ml/kg of either flower (1 : 10) or berry decoction (1 : 10) orally 2 h before and simultaneously with the investigated drugs injected subcutaneously. The hypnotic action of pentobarbitone in the animals as the onset of loss of righting reflex (sleep induction time) was assessed as the time interval between the loss and regaining of righting reflex (sleeping time). The analgesic action of morphine was measured as the reaction time to radiation heat directed onto the rat tail. Both decoctions caused a significant decrease of the sleep induction time of pentobarbitone, and increased sleeping time, compared with control (only pentobarbitone). Berry decoctions significantly decreased the analgesic action of morphine.     

The lack of effect of opioid agonists and antagonists on some acute effects of ethanol

We studied the ability of opioid antagonists: naloxone, naltrexone and diprenorphine and an opioid agonist morphine to influence the effects of ethanol on hypothermia, sleeping time and impairment of aerial righting reflex. Naltrexone (2-16 mg/kg) and naloxone (2-16 mg/kg) were not able to attenuate effects of ethanol, while diprenorphine decreased ethanol sleeping time (4 microgram/kg) and antagonized the ethanol hypothermia (8 microgram/kg). Naltrexone in a dose of 8 mg/kg sc antagonized the ethanol impairment of aerial righting reflex. The present behavioral studies did not provide any evidence for the participation of the opioid system in the mediation of acute ethanol effects in rats.     

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。     

加锡果宁的中枢抑制作用

加锡果宁(Ed)在1/20～1/8 LD_(50)剂量下对小鼠可明显缩短巴比妥或安定的翻正反射消失潜伏期和延长睡眠时间,增强乙醚的麻醉作用,减少自发活动。对某些镇痛药也有增强作用,使家兔脑电呈高幅慢波。延长大鼠总睡眠和慢波睡眠时间,与ip 30mg/kg戊巴比妥钠的作用强度相似,但Ed抑制异相睡眠时间比戊巴妥钠更强。     

The effect of electrostimulation on barbiturate-induced sleeping times in rats

Female rats, anaesthetized with hexobarbital, regained their righting reflex more rapidly following electrostimulation than sham-treated controls. The extent of the decreased sleeping times in these animals varied according to the frequency (cycles per second) of the electrostimulation applied. The frequency which produced the largest decrease in sleeping time was 10 Hz. Determination of the activity of some microsomal enzymes indicated that the decreased sleeping time was not the result of increased hepatic enzyme activity. Animals which had received prior treatment with naloxone exhibited increased sleeping times following barbiturate administration, but the effects of electrostimulation on the sleeping time at 10 Hz was diminished, while the effect of electrostimulation at high frequency (500 Hz) was enhanced. Although repeated daily administration of hexobarbital progressively decreased sleeping times for all the animals, electrostimulation decreased the sleeping times of the treated rats by a similar percentage of the control animals on each successive day. Electrostimulation at a frequency of 10 Hz produced a significant decrease in serum corticosterone levels, whereas 500 Hz resulted in an increase.     

Neuropeptide S is a stimulatory anxiolytic agent: a behavioural study in mice

BACKGROUND AND PURPOSE: Neuropeptide S (NPS) was recently identified as the endogenous ligand of an orphan receptor, now referred to as the NPS receptor. In vivo, NPS produces a unique behavioural profile by increasing wakefulness and exerting anxiolytic-like effects. In the present study, we further evaluated the effects of in vivo supraspinal NPS in mice. EXPERIMENTAL APPROACH: Effects of NPS, injected intracerebroventricularly (i.c.v.), on locomotor activity (LA), righting reflex (RR) recovery and on anxiety states (measured with the elevated plus maze (EPM) and stress-induced hyperthermia (SIH) tests) were assessed in Swiss mice. KEY RESULTS: NPS (0.01-1 nmol per mouse) caused a significant increase in LA in naive mice, in mice habituated to the test cages and in animals sedated with diazepam (5 mg kg(-1)). In the RR assay, NPS dose dependently reduced the proportion of animals losing the RR in response to diazepam (15 mg kg(-1)) and their sleeping time. In the EPM and SIH test, NPS dose dependently evoked anxiolytic-like effects by increasing the time spent by animals in the open arms and reducing the SIH response, respectively. CONCLUSIONS AND IMPLICATIONS: We provide further evidence that NPS acts as a novel modulator of arousal and anxiety-related behaviours by promoting a unique pattern of effects: stimulation associated with anxiolysis. Therefore, NPS receptor ligands may represent innovative drugs for the treatment of sleep and anxiety disorders.