小鼠吗啡依赖纳洛酮催促戒断跳跃反应模型的建立

目的建立稳定的小鼠吗啡依赖纳洛酮催促戒断跳跃反应模型。方法小鼠连续皮下注射吗啡,以纳洛酮催促戒断跳跃反应为指标,调整吗啡给予天数(5,6,7,10d)、吗啡累积剂量(360,560,640,945,1100,1105,1200mg/kg)、每日给予吗啡的频数[一天二次(bid),一天三次(tid)]、纳洛酮催促紧前给予吗啡与否、以及纳洛酮剂量(10,20mg/kg),建立四个造模方案包括八个子方案。结果方案A、B2、C2吗啡组小鼠跳跃反应率未达100%;方案B1、C1、D2、D3、D4吗啡组小鼠跳跃次数变异系数较大。方案D1采用小鼠连续皮下注射倍增剂量的吗啡,tid×6d,每日每次剂量分别为5,10,20,40,80,160mg/kg;第7天皮下注射吗啡160mg/kg,3h后腹腔注射纳洛酮10mg/kg,吗啡组小鼠可产生显著的跳跃反应,与对照组比较差异有显著性(P<0.01),且变异系数小(CV为0.22),该方案吗啡依赖小鼠跳跃反应次数适度,离散度小。结论选用方案D1可建立稳定的小鼠戒断跳跃反应模型。     

Effects of haloperidol and amisulpride on motor and cognitive skill learning in healthy volunteers

Buprenorphine is a mu opioid partial agonist currently used as an analgesic, and being developed for the treatment of opioid dependence. The purpose of this study was to determine the abuse liability of parenteral buprenorphine in volunteers maintained on daily sublingual (SL) buprenorphine (8 mg). In a residential laboratory, eight volunteers underwent pharmacologic challenges two times per week. Medication challenges were 16 h after the daily dose of buprenorphine, and consisted of double-blind IM injections of buprenorphine (4, 8, 16 mg), the prototypic mu opioid agonist hydromorphone (9 and 18 mg), or saline. Assessments consisted of physiologic monitoring, subjects’ self-reports, and a trained observer’s ratings of drug effects, and were collected for 0.5 h before and 2.0 h following injection. Supplemental doses of IM buprenorphine produced opioid agonist-like effects, indicating some abuse potential of parenteral buprenorphine in buprenorphine-maintained patients. There was incomplete cross-tolerance to the effects of hydromorphone, suggesting that higher maintenance doses of buprenorphine may be needed to maximize clinical efficacy. However, there was a lack of graded dose-effects for hydromorphone, suggesting that buprenorphine’s combination of partial agonist effects and high affinity for opioid receptors may limit the magnitude of effects of supplemental full agonists. Finally, participants tolerated cumulative doses of maintenance buprenorphine plus challenge buprenorphine without adverse effects, suggesting higher doses of buprenorphine can be safely administered to opioid dependent patients. Received: 22 February 1996/Final version: 23 August 1996     

Stimulus functions of drugs and the assessment of abuse liability

The development of a unifying framework for conceptualizing the commonalities in various forms of substance abuse must encompass the data base focused upon the stimulus functions of drugs. In the first instance, for example, the research on drug self-administration has provided convincing evidence of a remarkable concordance between laboratory animals and human substance abusers in the reinforcing stimulus functions of a range of chemical agents. The recognition of these cross-species and cross-drug generalities has radically changed conceptualizations of substance abuse from a reactive to a more active process and has encouraged the kind of functional analysis of drug-seeking and drug-taking that has proven productive and useful in the study of other behavioral interactions. In this regard as well, recent refinements in the analysis of the discriminative stimulus functions of drugs have provided a more comprehensive basis for characterizing a chemical agent's spectrum of action and evaluating its abuse liability. While the correlation between the discriminative stimulus functions and the reinforcing stimulus functions is remarkably high for some drug classes, there are notable exceptions. Finally, the assessment of abuse liability requires an analysis of the eliciting stimulus functions of drugs as reflected by the physiological and behavioral changes, both acute and chronic, that follow drug administration. The methods used to evaluate both physiological dependence and behavioral toxicity in relationship to sensory and motor effects for a range of abused drugs have depended heavily upon an assessment of the eliciting stimulus functions of such compounds.     

山莨菪碱治疗麻醉剂依赖性

阿片成瘾者２５０例（男性２２２例，女性２８例，年龄３０±ｓ５ａ）应用山莨菪碱０．５－２ｍｇ／（ｋｇ·ｄ），分２－３次加入１０％葡萄糖２５０ｍＬ或５％葡萄糖生理盐水５００ｍＬ静脉滴注；东莨菪碱０．０２－０．０３ｍｇ／ｋｇ加入１０％葡萄糖２５０ｍＬ静脉滴注１次，必要时对重患者追加１次，疗程５－７ｄ。结果戒断症状均有改善（Ｐ＜０．０１），２７例需加用羟丁酸钠。不良反应轻，可作为阿片瘾者的脱瘾药物。＊Ｐ＜０．０１。碱确能解除阿片药物戒断症状。其对阿片戒断症状缓解时间在治疗４－５ｄ后，强烈觅药渴求也随之逐渐消失。１５０例（６０％）要求进食，１７５例（７０％）仍需借助安眠药睡眠。另６５例（２６％）戒断症状阵发性发作，每次持续０．５－１ｈ，症状轻重不一，轻者流泪、全身弥漫性疼痛，重者焦躁不安、心中猫抓虫咬样难受，甚至想自残，可配合艾司唑仑３－４ｍｇ／ｄ，ｐｏ或氯硝西泮６－１０ｍｇ／ｄ，ｐｏ；也可用氯硝西泮１－２ｍｇ／次，ｉｍ，每日２－３次；针刺胃俞、脾俞、中脘、足三里、印堂、太阳、百会、内关、合谷、命门、夹脊和肾俞穴位，根据临床症状任选其中３－５个穴位进行治疗或心理治疗能快速减轻患者戒断症状。治程中２７例（１０．８％）重?     

A programme for treating chemically dependent medical students

Summary. The first American programme for chemically dependent medical students at the University of Tennessee, Memphis is described. The goals of the Aid for the Impaired Medical Student (AIMS) Program are to provide confidential treatment for chemically dependent medical students, to assure that recovering students are able to resume their education, and to protect patients and others from the harm that may be caused by impaired students. The Program is administered by the AIMS Council, consisting of medical professionals and elected student representatives. The Council oversees the management of cases, including investigation of students who may be impaired, intervention when chemical dependency is suspected, diagnostic evaluation, treatment and aftercare, and post-recovery advocacy for students. The Program's experience includes 18 cases of suspected chemical dependency, with four self-referrals and 14 students referred by third parties. Eleven students have been diagnosed as chemically dependent and have completed treatment programmes. Nine have maintained recovery and eight have graduated. One student subsequently relapsed and committed suicide. Obstacles in programme implementation have involved absence of perceived need, the view that chemically dependent students should be dismissed from school, and reluctance of students to report classmates. Resources have included highly respected student representatives, a supportive administration, assistance of the impaired physicians programme, and medical insurance and professional courtesy to defray costs. Although the number treated has been modest, the AIMS Program is an important vehicle for training students regarding chemical dependency and their professional obligations toward impaired colleagues.     

Tolerance and dependence to opiates

In the 19th century, investigators recognized that addiction to opiates involves tolerance and dependence. In the United States, the National Academy of Sciences and the Public Health Service initiated systematic investigations into opiate addiction in 1929. Tolerance and dependence to morphine, the prototype for opiate drugs, were the emphasis of human studies for the next fifty years. This presentation highlights salient features of tolerance and dependence learned in these studies and relates these findings to clinical use in treating pain.     

New South Wales Nurse Education Project

Abstract: The development of a teaching package for nurse educators on drug and alcohol problems is described and the contents of its 16 modules outlined.     

Bupropion and nicotine patch as smoking cessation aids in alcoholics.

This is a double-blind placebo-controlled study of sustained-release bupropion as a smoking cessation aid in alcoholics undergoing treatment for their alcoholism. Participants (N=58) were enrolled within 1 week of entry into alcohol treatment from community and Veterans Affairs Substance Use Disorder programs. All participants received nicotine patch and were invited to attend a smoking cessation lecture and group. Cigarette smoking and alcohol outcomes were measured at 6 months. Bupropion when added to nicotine patch did not improve smoking outcomes. One third of participants on bupropion reported discontinuing the drug during weeks 1-4. Participants reported cigarette outcomes with nicotine patch that are similar to those seen in the general population. All study participants significantly reduced cigarette use. Comorbid affective disorder or antipersonality disorder did not affect outcomes. Alcohol outcomes were improved in those who discontinued cigarettes.     

Graduate Education in the Field of Substance Abuse

Abstract: Twenty-six part-time students from a variety of professional backgrounds are enrolled in the first year of a Graduate Diploma in Social Science (Drug Dependence) at the Phillip Institute of Technology in Victoria. The course is conducted under the auspices of the School of Social Work and commenced in 1984. It is argued that the graduates from this unique course could play a key role in providing personnel to fill positions in the areas of clinical work, staff development, drug education, programme development and management and research.