Behavioural tolerance to arecoline in rats: Cross-tolerance to oxotremorine and prevention by pretreatment with atropine

In two experiments tolerance development to the effects of arecoline on operant responding for a water reward was shown to be dose-dependent, complete tolerance developing to a daily dose of 4 mg/kg, but only partial tolerance developing to a daily dose of 8 mg/kg. However, rats chronically treated with the higher dose of arecoline were least affected by a challenge dose of oxotremorine (0.2 mg/kg); i.e. the high dose group exhibited the greatest cross-tolerance to oxotremorine. Moreover, atropine (4 mg/kg) pretreatment prior to arecoline (4 mg/kg) prevented cross-tolerance to oxotremorine, indicating that dispositional mechanisms are unlikely to be involved in tolerance to arecoline.     

Continuous exposure to the competitive <Emphasis Type="BoldItalic">N</Emphasis>-methyl-<Emphasis Type="SmallCaps">d</Emphasis>-aspartate receptor antagonist,LY235959, facilitates escalation of cocaine consumption in Sprague–Dawley rats

Rationale Chronic high dose consumption of cocaine is associated with significant negative effects to individual users and society. Nevertheless, the precise mechanisms that mediate increases in cocaine consumption in a drug-using individual are not fully understood. Objectives This study used a long access version of the drug self-administration procedure to determine whether escalation of cocaine consumption is mediated by increased activity through N-methyl-d-aspartate (NMDA) receptors. Materials and methods Male Sprague–Dawley rats (n = 63) were first trained to self-administer cocaine (0.33 mg/infusion, i.v.) under a fixed-ratio 1 schedule of reinforcement. After training, some rats were implanted with subcutaneous osmotic minipumps filled with vehicle or the competitive NMDA receptor antagonist, LY235959, and subsequently allowed to self-administer cocaine in short (2 h) or long (6 h) access self-administration sessions. Results Vehicle-treated rats escalated cocaine self-administration across 14 long-access self-administration sessions. Rats treated with LY235959 via osmotic minipump, but not twice daily injections, escalated cocaine self-administration at a greater rate and to a greater degree than vehicle-treated rats. In post-escalation cocaine dose-infusion tests, rats treated continuously with LY235959 self-administered more cocaine (0.08–1.32 mg/infusion) than vehicle-treated rats, regardless of access condition, shifting the dose-infusion curves upward. During extinction sessions, which were conducted after the escalation phase of the study, rats that had long (6 h) access to cocaine stopped responding sooner than rats that had short (2 h) access to cocaine, independent of LY235959 treatment. Conclusions These data are consistent with hypo-glutamatergic consequences of repeated cocaine exposure. Preliminary reports of these data were presented at the 2003 meeting of the Society for Neuroscience (New Orleans, LA) and the 2005 meeting of the College on Problems of Drug Dependence (Orlando, FL).     

强脉冲光联合睑板腺按摩与眼睑熏蒸按摩治疗MGD相关干眼的疗效对比

目的：观察对比强脉冲光(IPL)联合睑板腺按摩与眼睑熏蒸按摩对睑板腺功能障碍(MGD)相关干眼的治疗效果。

方法：本研究为前瞻性随机对照临床试验。选取2018-03/08在西安市第四医院干眼门诊就诊的73例146眼MGD相关干眼患者,试验组38例76眼,给予IPL联合睑板腺按摩治疗(每3wk 1次,共3次)。对照组35例70眼给予眼睑熏蒸联合睑板腺按摩治疗(每天熏蒸、清洗睑缘,连续5d,第5d进行睑板腺按摩,间隔2wk后再次重复治疗,共3次)。本研究时间共12wk,记录首次治疗前及首次治疗后1、4、7、12wk时患者的眼表疾病指数(OSDI)评估、标准干眼评估问卷(SPEED)、非侵入泪膜破裂时间(NITBUT)、非侵入泪河高度测量(NITMH)、睑板腺缺失积分(MGS)、睑板腺分泌物评估(MGYSS)等数据,评估两种治疗方法的有效性及二者的疗效对比。

结果：两组间性别、年龄无差异(P>0.05)。两组治疗前各观察指标无差异(P>0.05); 两组治疗后各时间点除NITMH、MGS外各项指标均较治疗前有明显改善(P<0.05)。试验组在治疗后1wk时各项指标与对照组无差异(P>0.05); 试验组在治疗后4、7、12wk时,除NITMH、MGS外均优于对照组(P<0.05)。从指标变化趋势上看,试验组于首次治疗后疗效指标持续好转,于第12wk时疗效最佳,而对照组于首次治疗后第7wk疗效最佳,之后疗效减弱。治疗后两组均未见明显并发症。

结论：强脉冲光联合睑板腺按摩及眼睑熏蒸按摩两种治疗方式均对MGD相关干眼治疗方便、安全、有效,且强脉冲光联合睑板腺按摩疗效及维持时间优于眼睑熏蒸按摩治疗。     

三种置管用于治疗泪道阻塞效果比较

目的：比较采用泪道逆行置管、双套环顺行置管、泪道U形置管治疗泪道阻塞患者的治疗效果。

方法：前瞻性研究。选取2015-07/2018-06在我院诊治的108例108眼泪道阻塞患者,随机分为三组,A组行泪道逆行置管术36例36眼,B组行双套环顺行置管术36例36眼,C组行泪道U形置管术36例36眼,术后随访6mo,比较三组患者术中出血量、手术时间、住院时间、治疗疗效以及并发症和泪道阻塞复发情况。

结果：三组患者术中出血量、手术时间、住院时间比较差异有统计学意义(P<0.05)。A组的治疗总有效率为91.7%,B组为94.4%,C组为97.2%(P>0.05)。A组并发症发生率为11.1%,高于B组的5.6%,高于C组的2.8%(P=0.010); A组泪道阻塞复发率为9.1%,高于B组的5.9%,高于C组的5.9%(P=0.029)。

结论：泪道逆行置管、双套环顺行置管、泪道U形置管用于治疗泪道阻塞患者的疗效均较高,术后发生并发症和泪道阻塞复发较少,但泪道逆行置管术可减少术中出血量、手术时间,泪道U形置管术可减少患者住院时间。     

Characteristics of ethanol tolerance in alcohol drinking (AA) and alcohol avoiding (ANA) rats

The development of tolerance to ethanol was examined in two rat lines selected for high (AA) and low (ANA) ethanol consumption. In the first experiment, the acquisition of tolerance to the motor-impairment, hypothermic and hypnotic effects of ethanol produced by daily treatment with 5 g/kg ethanol for a period of 24 days was examined. Tolerance to these effects of ethanol was observed in the AA rats while marginal or no tolerance was demonstrated in the ANA rats. In the second experiment the development of rapid tolerance to the hypothermic and hypnotic effects of ethanol was examined. The hypothermic and hypnotic responses to IP injection of 3.5 g/kg ethanol were found to be attenuated in the AA but not the ANA rats by a single equivalent ethanol injection given 24 h earlier. These results suggest some relationship between the capacity to develop tolerance and voluntary ethanol intake.     

Nicotine tolerance: an analysis of the time course of its development and loss in the rat

The time course of the development and loss of tolerance to nicotine was measured in female rats that were injected subcutaneously (SC), twice daily with 1.6 mg/kg nicotine. Tolerance to nicotine-induced decreases in locomotor activity and body temperature were observed. Tolerance to the effects of nicotine on both of these measures developed rapidly, with maximal changes occurring within 2–4 days after initiation of treatment. The binding ofl-[³H]-nicotine was measured in six brain regions. Chronic nicotine treatment resulted in increases in binding in most brain regions. The increase in binding correlated significantly with the development of tolerance. Rats that had been injected chronically with nicotine did not lose their tolerance throughout a 7-day post-treatment test period. Control levels of binding were regained in all of the brain regions except cortex by 7 days after nicotine treatment was stopped. These findings indicate that changes in receptor binding may relate to the development of tolerance but the retention of tolerance is clearly not related to the number of brain nicotinic receptors, unless nicotine-induced decreases in body temperature and locomotor activity are controlled by cortical [³H]-nicotine binding sites.     

Dependence and cross-dependence in the guinea-pig myenteric plexus

Summary Chronic activation of opioid receptors results in the development of tolerance and dependence. Tolerance may be confined to a single receptor type and thus has been termed selective tolerance. The present investigation reveals that prolonged activation of an inhibitory acting receptor type not only results in dependence associated with this receptor but also brings about cross-dependence. Cross-dependence involves both opioid receptors as well as non-opioid receptors, e. g. adrenoceptors. The experimental design employed did not permit conclusions to be drawn about whether those receptors exhibiting cross-dependence also developed tolerance. Regardless of the receptors and their specific subsequent transduction systems, all the receptors which showed dependence and cross-dependence proved sensitive to pertussis toxin, suggesting a critical function of GTP-binding proteins for the development of not only opioid dependence but also for drug dependence in general. Since multiple transmitter receptors may converge on the same ion channel, the concept of convergent dependences may be linked to GTP-binding proteins. However, no conclusions can be drawn with regard to the precise biochemical mechanisms underlying dependence. Send offprint requests to R. Schulz at the above address     

Chronic administration of a selective dopamine D-2 agonist: factors determining behavioral tolerance and sensitization

The locomotor stimulant effects of sustained administration of a potent and selective dopamine (DA) D-2 receptor agonist, [+]-4-propyl-9-hydroxynaphthoxazine (PHNO), in rats were assessed 24 h a day during 12 h light-dark cycles. PHNO was administered continuously with subcutaneous implants of Alzet osmotic minipumps (5 g/h), for 12 h a day with modified osmotic minipumps (5 g/h), or by daily injections (15 g, SC). Tolerance was observed to occur only with 24 h continuous infusions and only during the light period. The other treatment regimens produced sensitization of the locomotor response. Daytime tolerance to continuous infusions of PHNO was reversed following reversal of the light-dark cycle. A normally arousing stimulus also reversed (temporarily) daytime tolerance. The present results indicate that the temporal pattern of administration of DA agonists, the phase of the circadian cycle and environmental stimuli associated with arousal are important determinants of the behavioral consequences of long-term treatment.     

幽门螺杆菌处理前后HepG2细胞蛋白质双向电泳图谱的差异分析

目的:利用蛋白质组学方法,识别并鉴定幽门螺杆菌(Helicobacterpylori,H.pylori)处理HepG2细胞后差异表达的蛋白质,为进一步探讨幽门螺杆菌对肝细胞的病理作用机制奠定基础。方法:运用固相pH梯度双向凝胶电泳技术分离H.pylori处理前后HepG2细胞的总蛋白质,用图象分析软件比较分析,以识别差异表达的蛋白质;应用质谱仪(massspectrometry)得到相应的肽质指纹图谱(peptidemassfingerprint,PMF),然后搜索数据库鉴定差异蛋白质。结果:鉴定出12种差异表达蛋白质,这些蛋白质包括整合素β1、蛋白激酶Cα、PINCH蛋白、Ras相关蛋白Rab37、LIM同源盒蛋白Lhx1、HLAⅠ类抗原、血管抑制素和金属蛋白酶抑制因子2等。这些差异蛋白质涉及基因表达调控、细胞免疫、细胞生长和信号传导等众多关键事件。结论:H.pylori处理前后HepG2的蛋白质组具有差异,这些差异表达的蛋白质可能参与了H.pylori对肝细胞的病理作用过程,这种蛋白质组的差异分析有助于进一步研究H.pylori与人类肝脏疾病的关系。     

颅骨及脑组织CT MR显示差异对脑肿瘤放疗剂量学影响的研究

目的:研究颅骨及脑组织CT/MR显示差异对脑瘤放疗剂量学的影响.方法:选取60例接受放疗的脑转移瘤(brain metasta?ses,BM)患者,每例患者均行CT和MR模拟定位,将CT图像和MR图像刚性配准,在CT/MR融合图像上勾画肿瘤靶区、危及器官、颅骨(分别命名为Skull-CT、Skull-MR)、脑组织(分...