THE EFFECT OF CHLORPROMAZINE PRETREATMENT ON MORPHINE ANALGESIA AND NALOXONE POTENCY IN ADRENALECTOMIZED MICE

Morphine pretreatment (2.0 mg/kg s.c.) induced no overt tolerance to its antinociceptive effect in mice 3 h later, but enhanced the antagonistic potency of naloxone. 2 Pretreatment with chlorpromazine slightly potentiated the antinociceptive effect of morphine measured 3.5 h later. The antagonistic effect of naloxone was also enhanced. 3 The observed effect of chlorpromazine on naloxone potency was augmented when naloxone was administered in the pretreatment regime. 4 The enhanced naloxone potency induced by morphine pretreatment was inhibited by chlorpromazine administered 0.5 h before the morphine pretreatment. 5 Adrenalectomy sensitized the animals to the antinociceptive effect of morphine. However, the naloxone potency was similar to that of the sham-operated controls. 6 Adrenalectomy greatly attenuated the effect of chlorpromazine pretreatment on naloxone potency. However, the effect of combined pretreatment with either chlorpromazine plus naloxone or morphine remained unaffected. 7 These results indicate that the increased naloxone potency after chlorpromazine pretreatment may be partly mediated through an adrenal-linked process. However, it appears that this process is not essential for the development of increased naloxone potency induced by morphine pretreatment and for the interaction between chlorpromazine, naloxone and morphine.     

甲氧氯普胺对小鼠吗啡身体依赖性的影响

目的·· :观察甲氧氯普胺对吗啡身体依赖性的影响。方法·· :皮下注射盐酸吗啡建立吗啡依赖小鼠模型,以纳洛酮催促戒断症状。分别在建立吗啡依赖模型前或后给予不同剂量的甲氧氯普胺,观察其预防性给药和急性给药产生的影响。结果·· :甲氧氯普胺急性给药(20 -80mg·kg-1,ip)吗啡依赖小鼠跳跃次数显著减少 ,体重下降加剧 ;预防性给药 (5-20mg·kg-1,ip)小鼠跳跃次数减少 ,但无统计学意义 ,体重下降有显著性改善。结论·· :甲氧氯普胺可缓解吗啡依赖小鼠的部分戒断症状,在一定程度上抑制吗啡身体依赖的形成。     

SEX DIFFERENCES AND THE EFFECT OF GONADECTOMY ON MORPHINE-INDUCED ANTINOCICEPTION AND DEPENDENCE IN RATS AND MICE

1. Differences between sexes and the effect of bilateral surgical gonadectomy on the response to morphine analgesia and dependence were examined in rats and mice. 2. The analgesic response to morphine (5 mg/kg) was assessed by the hot plate and the abdominal constriction tests. Dependence was induced by injecting morphine at increasing doses (5–160 mg/kg) for 6 consecutive days and withdrawal signs elicited by injecting naloxone (2.5 mg/kg). 3. The base line reaction times in the intact control, shamoperated and gonadectomized animals of either sex were not significantly different from each other. 4. After treatment with morphine, the percentage increase in the reaction time in gonadectomized male and female rats and in gonadectomized male mice was significantly higher than in their respective controls. 5. The increase in the reaction time, after morphine treatment, was significantly higher in gonadectomized female rats than in gonadectomized male rats. 6. Naloxone-induced withdrawal signs in morphine-dependent gonadectomized rats and mice were not significantly different from those in sham-operated controls. However, female rats in both groups exhibited a significantly higher number of escape jumping responses than males.     

HYPOTHERMIA ENHANCES THE EFFECTS OF MORPHINE ON HORMONAL AND HISTAMINE RELEASE

1. The effects of intravenous (i.v.) morphine on adrenocorticotrophic hormone (ACTH), beta-endorphin (beta-END), total catecholamines (CA) and histamine (HIS) plasma concentrations, were determined in anaesthetized dogs at 30 degrees C and 37 degrees C. 2. Hypothermia initially increased CA levels by 29%, but the values returned to baseline after 2 h. Morphine (1 mg/kg, i.v.) produced a significant decrease in CA both at 37 degrees C and 30 degrees C (34% and 54%, respectively). Subsequent administration of naloxone (1 mg/kg, i.v.) significantly increased CA levels in both groups. 3. Hypothermia per se had no effect on ACTH, beta-END, and HIS concentrations. Morphine produced a significant increase in pituitary hormones and HIS, in hypothermic but not in normothermic animals. Morphine concentrations were significantly higher at 30 degrees C during the first 45 min. 4. The results suggest that the effects of morphine on hormonal and histamine release observed at 30 degrees C are concentration-dependent and related to changes in morphine pharmacokinetics.     

DIFFERING EFFECTS OF THE VASODILATOR DRUGS, PRAZOSIN AND DIAZOXIDE ON PLASMA RENIN ACTIVITY IN THE DOG

1. The effects of intravenous (i.v.) administration of the vasodilator drugs prazosin or diazoxide on blood pressure and plasma renin activity were evaluated in the anaesthetized dog. 2. Prazosin and diazoxide both induced a rapid reduction in the mean arterial pressure to 73% and 75% of control values respectively. 3. Prazosin Iowered plasma renin activity to 62% (P < 0.025) of the control value whereas diazoxide raised plasma renin activity to 178% (P < 0.05) of the control value. 4. The combination of vasodilatation and low renin activity observed following the administration of prazosin is unique, and may have clinical significance if these factors reduce the vascular complications of hypertension.     

褪黑激素抑制小鼠吗啡戒断反应并降低血浆、脑组织中NO含量

目的观察褪黑激素(MT)对小鼠吗啡戒断反应及血浆、脑组织中NO含量的影响。方法定量吗啡sc,建立小鼠吗啡依赖模型;纳洛酮ip催瘾。用褪黑激素连续ig 3 d。根据小鼠戒断反应中出现跳跃反应的潜伏期、跳跃次数、体重丢失评定戒断反应强度。用硝酸还原酶法检测血浆和脑组织中NO含量。结果用褪黑激素ig可明显延长小鼠吗啡戒断跳跃反应的潜伏期、减少跳跃次数, 对体重丢失也有所改善。MT可抑制由戒断反应引起的血浆和脑组织中NO含量的升高。结论褪黑激素可抑制小鼠吗啡戒断反应并降低由戒断反应引起的血浆和脑组织中NO含量的升高。     

THE EFFECT OF CHLORPROMAZINE PRETREATMENT ON THE NARCOTIC ANTAGONISTIC POTENCY OF NALOXONE IN MICE

Morphine pretreatment (8.0 mg/kg s.c.) induced no overt tolerance to its antinociceptive effect in mice 4 h later, but enhanced the antagonistic potency of naloxone. Pretreatment with chlorpromazine hydrochloride (0.5–2.0 mg/kg s.c.) potentiated the antinociceptive effect of morphine measured 4.5 h later. The antagonistic effect of naloxone was also enhanced. The observed effect of chlorpromazine on naloxone potency was augmented when naloxone hydrochloride 0.2 mg/kg was administered in the pretreatment regime. The enhanced naloxone potency induced by morphine pretreatment was inhibited by chlorpromazine administered 0.5 h before the morphine pretreatment. These results indicate that pretreatment with either morphine or chlorpromazine increased the antagonistic potency of naloxone. However, it appears that these two drugs act by different mechanisms.     

地尔硫抑制小鼠吗啡戒断反应及血浆和脑匀浆一氧化氮的含量

目的··:观察钙拮抗剂盐酸地尔硫对小鼠吗啡戒断反应及血浆和脑匀浆一氧化氮 (NO)含量的影响。方法··:皮下注射定量吗啡 ,建立小鼠吗啡依赖动物模型 ;腹腔注射纳洛酮催促 ,根据小鼠戒断反应中出现跳跃反应的潜伏期、跳跃次数和体重丢失评定戒断反应的强度 ;用硝酸还原法检测其血浆和脑内NO含量。结果·· :3种不同剂量 (25、50、100mg·kg-1)的盐酸地尔硫对小鼠吗啡戒断反应有明显的抑制作用 ,并呈量效关系;100mg·kg-1的盐酸地尔硫可抑制吗啡戒断反应引起的血浆和脑匀浆NO含量的升高。结论·· :盐酸地尔硫可抑制小鼠吗啡戒断反应 ,并能抑制戒断反应引起的血浆和脑匀浆NO含量的升高。     

褪黑素对吗啡戒断大鼠脑内cAMP和cGMP含量的影响

目的 :观察褪黑素 (MT)对吗啡戒断大鼠不同脑区cAMP和cGMP含量的影响。方法 :以剂量递增法连续皮下注射吗啡建立吗啡依赖模型 ,采用放射免疫学方法测定脑内cAMP和cGMP的含量。结果 :(1)MT对大鼠吗啡戒断症状具有明显的抑制作用 ;(2 )与对照组比较 ,吗啡依赖大鼠的纹状体、间脑、中脑、脑桥和海马内cAMP含量显著增高 (P <0 0 5 ,P <0 0 1) ,cGMP含量显著下降 (P <0 0 5 ,P <0 0 1)。与吗啡依赖组比较 ,催促戒断大鼠海马和纹状体内cAMP的含量显著升高 (P <0 0 5 ) ,而cGMP含量显著下降 (P <0 0 5 ,P <0 0 1) ,其他部位则无明显变化 ;(3)褪黑素急性治疗可使吗啡戒断大鼠纹状体、间脑、中脑、脑桥和海马内cAMP含量明显下降 (P <0 0 5 ,P <0 0 1) ,cGMP含量明显增高 (P <0 0 5 ,P <0 0 1)。结论 :MT可显著抑制大鼠吗啡戒断反应 ,并与调节中枢cAMP和cGMP含量有关。     

EFFECTS OF HISTAMINE AND HISTAMINE ANTAGONISTS ON HEPATIC BILE FLOW IN THE CONSCIOUS SHEEP

The effects of histamine and histamine antagonists on bile flow have been studied using the cholecystectomized conscious sheep. Histamine stimulated bile flow in a dose-dependent manner (D50 = 15.7 micrograms/h per kg). Free water and HCO3-output were increased after intravenous histamine infusion. With histamine at 120 mg/h per kg, there was a 41.0 (s.d. = 4.6)% and 38.7 (s.d. = 4.2)% (n = 6) increase in bile volume and HCO3-output respectively. Bile salt concentration was decreased after intravenous histamine, but net bile salt secretory rate remained unchanged. There was no change observed in the molar ratios of bile salts: phospholipids: cholesterol. Total lipids were decreased from 2.2 (s.d. = 0.3) to 1.60 (s.d. = 0.4) g/dl (n = 6). The corrected lithogenic index did not change significantly. 14C-Erythritol clearance also increased during histamine infusion in a dose-dependent manner but did not correspond to increments in bile flow. The histamine H1-receptor antagonist, diphenhydramine 0.05-1.0 mg/h per kg did not alter histamine stimulated bile flow. The H2-receptor antagonists, cimetidine (0.5-4 mg/h per kg) and ranitidine (0.05-0.5 mg/h per kg) progressively reversed the histamine-induced choleresis. Maximum inhibitory effect was attained at 2.0 and 0.25 mg/h per kg for cimetidine and ranitidine, respectively. At these levels, variation of intravenous infusion of histamine did not result in competitive displacement of the inhibitory response by either cimetidine or ranitidine. Moreover, concomitant infusion of diphenhydramine at 1.0 mg/h per kg potentiated the inhibitory effect of cimetidine or ranitidine on histamine-induced choleresis. Histamine increases the bile salt independent component of hepatic bile flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

皮质酮对吗啡条件性位置偏爱及条件性精神运动获得的影响

目的 :研究皮质酮作用下吗啡条件性位置偏爱 (CPP)及条件性精神运动的变化趋势及其可能机制 ,为探讨应激、环境线索诱发复吸的机制提供基础。方法 :32只♂SD大鼠分成 4组。训练 2d ,1次药物匹配训练 (吗啡 2mg·kg- 1 ,皮质酮 5mg·kg- 1 ,ip ,提前 2 0min注射 ) ,1次生理盐水训练。观察训练前后大鼠在伴药侧停留的时间 ,急性给药后的运动及条件性精神运动的变化。结果 :(1)吗啡组训练后在伴药侧停留的时间显著长于对照组 (P <0 0 1) ,皮质酮吗啡组、皮质酮组与对照组比较差异无显著性 (P >0 0 5 ) ;(2 )在 5 0、6 0min时皮质酮吗啡组的急性精神运动显著大于吗啡组和对照组 (P <0 0 1) ;(3)皮质酮吗啡组大鼠的条件性精神运动显著大于对照组、吗啡组 (P <0 0 1,P <0 0 5 )。结论 :5mg·kg- 1 的皮质酮显著抑制吗啡CPP的获得 ,但促进吗啡条件性精神运动的获得以及急性精神运动。CPP与条件性精神运动获得的机制可能存在差异     

褪黑素对吗啡依赖小鼠肝损害的治疗作用

目的··:探讨褪黑素对吗啡依赖小鼠肝组织损害的治疗作用。方法·· :用皮下定量注射吗啡的方法建立吗啡依赖小鼠模型 ,经褪黑素治疗4周后 ,用HE染色、酶组织化学染色及图像分析方法 ,在光镜下观察吗啡依赖小鼠肝脏组织结构及酶组织化学变化。结果··:肝细胞变性的发生率在吗啡自然戒断组为10例 (10/10) ;ACP、LDH活性升高 ,而SDH活性降低。褪黑素治疗组仅1例 (1/10) ,且为个别肝细胞水肿 ;ACP、LDH和SDH活性正常。结论·· :褪黑素可使吗啡所致的肝损害得到良好恢复     

济泰片对吗啡损伤小鼠免疫功能的影响

目的:观察济泰片对吗啡损伤小鼠免疫功能的影响。方法:皮下注射(sc)吗啡建立吗啡依赖小鼠模型。称量胸腺、脾脏重量。采用碳粒廓清实验,二硝基氟苯(DNFB)诱导小鼠迟发性变态反应(DTH)实验和血清溶血素测定,观察济泰片对吗啡损伤小鼠免疫器官指数、非特异性和特异性免疫功能的影响。结果:济泰片0.30 g(原粉).kg-1和0.60 g(原粉).kg-1能显著升高吗啡损伤小鼠廓清指数(K)和吞噬指数(α)(P<0.05,P<0.01),耳肿胀度(P<0.01)和半数溶血值(HC50),并且能显著抑制免疫器官的萎缩。结论:济泰片能显著增强吗啡损伤小鼠的免疫功能。     

伏隔核电刺激对大鼠吗啡条件性位置偏爱重现的影响

目的:为寻找防治药物依赖新方法,本文以大鼠条件性位置偏爱(CPP)为模型,探讨伏隔核电刺激对阿片类物质奖赏效应的影响.方法:20只成年大鼠分为两组:深部脑刺激(deep brain stimulation,DBS)组和假DBS组.用立体定位手术将DBS装置的电极部分植入一侧伏隔核(NAc)核心部,与脉冲发生器(IPG)...     

EFFECTS OF HISTAMINE RECEPTOR ANTAGONISM ON ADRENALINE-INDUCED CHANGES IN BLOOD PRESSURE IN INTACT DOGS

This study was designed to test the hypothesis that histamine may contribute to the vasodepressor response which occurs in response to physiologic increments in adrenaline concentration in intact animals. Accordingly, following a control period of 30 min, adrenaline was infused intravenously for 45 min at a rate of 250 ng/kg per min in 14 anaesthetized dogs (Group I). A second group of eight dogs received an identical adrenaline infusion following complete H1- and H2-histamine receptor antagonism with tripelennamine plus cimetidine (Group II). A time control group of experiments, in which no drugs were infused, as well as groups receiving adrenaline plus either tripelennamine or cimetidine, were also performed. In Group I, adrenaline infusion increased heart rate and reduced mean arterial blood pressure by 10 mmHg (P less than 0.01). Following combined H1- and H2-histamine receptor antagonism (Group II), adrenaline infusion failed to reduce mean arterial blood pressure. However, mean arterial blood pressure was reduced significantly in the groups receiving adrenaline plus only one of the histamine receptor blocking agents. Since only the combined histamine receptor blockade completely eliminated the vasodepressor response to adrenaline, the data suggest that histamine may play a physiological role in the vasodepressor response to circulating adrenaline in the intact animal, and that both H1- and H2-histamine receptors may be involved.     

中药戒得安对吗啡依赖大鼠血清和尿中吗啡含量的影响

目的··:考察戒得安的戒毒机理。方法··:应用放射免疫法测定吗啡依赖大鼠血清和尿液中吗啡含量。结果·· :戒得安能显著增加依赖大鼠在停用吗啡后尿液及血清中吗啡的含量。结论··:戒得安具有加速体内毒品排出体外的速度,而达到脱毒的疗效     

IS FLEMING'S LYSOZYME AN ANALGESIC AGENT? EXPERIMENTS ON MICE

1. Antinociceptive activity of hen egg white lysozyme (Fleming's lysozyme) was determined against abdominal contractions provoked by irritants injected intraperitoneally into mice. Carrageenan (2 mg) (CA) injected with arachidonic acid (15 micrograms) (AA) or prostaglandins PGE1 or PGF2 alpha (0.04 ng), brewer's yeast (10 mg), caolin (10 mg), mepartricin (80 U) and phenylquinone (50 micrograms) were used as irritants. 2. Lysozyme was active at 400-800 mg/kg i.v. against CA + AA, CA + PG, brewer's yeast and caolin nociceptive stimulation. The compound was more effective against CA + AA than against CA + PG. Acetylsalicylic acid at 50-100-200 mg/kg p.o. was equally active against CA + AA and CA + PG. 3. Lysozyme was inactive in the tail pinch and hot plate tests that mainly detect central analgesics. 4. The results are discussed in relation to the claim advanced years ago that lysozyme is an effective analgesic agent in humans. The compound was found active against herpes zoster or cancer pain but did not find use despite the favourable reports presented. 5. The experimental results obtained on laboratory animals do not contradict the conclusions drawn after the clinical use of the compound.     

THE EFFECT OF APOMORPHINE AND CLONIDINE ON LOCOMOTOR ACTIVITY IN MICE AFTER LONG TERM TREATMENT WITH HALOPERIDOL

1. Mice were given haloperidol (approximately 3 mg.kg^?1 day^?1) or vehicle for 21 days and then withdrawn from the drug. All tests were performed 4 days after withdrawal. 2. Haloperidol treated mice (premedicated with reserpine plus a-methyl-p-tyrosine) displayed an increased locomotor response to apomorphine and to apomorphine plus clonidine, but neither haloperidol- or vehicle-treated animals revealed any stimulant response to clonidine. 3. In mice which had not been pretreated with reserpine plus a-methyl-p-tyrosine, clonidine produced a significant stimulation of locomotor activity in animals withdrawn from haloperidol but not in those withdrawn from the vehicle. Phen-oxybenzamine blocked the locomotor stimulant difference between these two groups, but did not completely antagonize the stimulant effect of clonidine in mice withdrawn from haloperidol. Pimozide was largely effective in blocking the clonidine-induced stimulation. Co-administration of phenoxybenzamine and pimozide was completely effective in blocking the stimulant effect of clonidine in mice withdrawn from haloperidol. 4. The evidence for a change in catecholamine receptor sensitivity was supported by the increased stimulant effect of dexamphetamine in the haloperidol-treated, compared to the vehicle-treated animals. 5. The data suggest that there is a change in the functional responsiveness of both adrenergic and dopaminergic receptors after withdrawal from long term haloperidol treatment.     

THE EFFECT OF ADRENALECTOMY ON THE DEVELOPMENT OF MORPHINE TOLERANCE AND PHYSICAL DEPENDENCE IN MICE

A molecular sieve morphine pellet implanted for 24 h induced measurable tolerance and physical dependence in mice. 2 Adrenalectomy sensitized the animals to the antinociceptive effect of morphine. However, the degree of tolerance induced by morphine pellet implantation was not significantly affected. 3 Quantitative assessment of naloxone-precipitated withdrawal symptoms showed that adrenalectomy slightly enhanced the development of physical dependence. 4 These results indicate that adrenalectomy has no effect on the rate of development of morphine tolerance but may be involved in the development of physical dependence.     

吗啡长时程作用下小鼠脑组织磷酸肌醇含量和PKC活性的变化

目的旨在进一步阐明阿片依赖中PLC-PKC信号系统的变化与作用。用小鼠吗啡依赖模型,观察脑组织磷酸肌醇含量、PKC活性变化。结果发现:纹状体IP及IP3、大脑皮质IP含量明显升高,二者磷酸肌醇总量显著增加;胞质可溶相PKC活性在大脑皮质及小脑明显升高,在纹状体显著下降。膜相PKC活性在纹状体明显升高,在小脑和海马明显降低;PKC抑制剂可抑制吗啡依赖的产生。结果提示,吗啡依赖小鼠纹状体磷酸肌醇含量的增加意味着PLC的活化,这可能与纹状体中PKC的激活有关,而该PKC的激活可能参与吗啡依赖的形成。