海洛因戒断与复吸对大鼠结肠5-羟色胺和 P物质表达的影响

目的 探讨海洛因戒断、脱毒和复吸期间5-羟色胺(5-HT)、P物质(SP)在大鼠结肠表达的变化.方法 将正常雄性SD大鼠35只,随机分为实验组15只、盐水对照组15只和正常对照组5只,实验组大鼠又分戒断组(HWG)、脱毒治疗组(MDG)和复吸组(HRG).取正常对照组、盐水对照组及实验组大鼠的结肠组织,采用免疫组织化学SABC法及图像分析方法进行研究.结果 戒断组和复吸组大鼠结肠内的5-HT-、SP-免疫反应(IR)细胞的平均灰度值低于正常及盐水对照组,免疫反应细胞计数增多,差异有统计学意义(P<0.05).脱毒治疗组与正常及盐水对照组比较,大鼠结肠内的5-HT-、SP-IR细胞的平均灰度值及细胞计数差异均无统计学意义(P>0.05).结论 在海洛因戒断、复吸期间,结肠分泌5-HT、SP增多;美沙酮脱毒治疗后,5-HT、SP的表达与正常组差异无显著性,提示结肠分泌的5-HT、SP参与了海洛因戒断、脱毒和复吸期间机体的调节.     

大鼠海洛因中毒性脑损害病理与MRI的实验研究

目的通过动物实验探讨海洛因中毒性脑损害的病理特征及其MRI诊断价值。方法Wistar大鼠共40只,数字法随机分为海洛因注药组(简称注药组,共32只)及盐水对照组(简称对照组,共8只)。海洛因剂量逐日依次递增05mg/kg的整数倍,3次/d,腹腔注射,建立海洛因依赖大鼠模型和海洛因中毒性脑损害大鼠模型。同样方式注射不含海洛因的生理盐水建立对照组。注射纳洛酮后应用改进的柳田知司评分标准判断成瘾强度。2组大鼠在6个不同时期(累加剂量分别为918、1580、2686、3064、4336及4336mg/kg戒断2周)分别进行脑部的MR、光学显微镜(简称光镜)及电子显微镜(简称电镜)检查。结果第15天注药组和对照组大鼠戒断评分为(230±44)分和(14±05)分,统计学处理表明两组间差异具有统计学意义(t=9737,P<001),标志海洛因依赖大鼠模型建立成功。从累加剂量1580mg/kg开始至最高累加剂量4336mg/kg(第80天),注药组大鼠大、小脑均可见神经细胞变性坏死,表明海洛因中毒性脑损害大鼠模型建立成功。大鼠海洛因中毒性脑损害具体表现(1)大脑皮质神经细胞变性坏死和数量减少,呈典型“红色神经元”。光镜下,单因素方差分析表明,海洛因累加剂量4336mg/kg组与1580mg/kg组或对照组之间,大脑皮质神经细胞变性坏死数的差异具有统计学意义(P=0024及P=0032)     

环境线索对戒断期海洛因依赖者神经电生理的影响

Objective To explore the changes of craving and neuro-electrophysiological reactions under the exposure of heroin-related cues in abstinent heroin dependents.Methods In this self-controlled study,382 abstinent heroin dependent patients watched video of heroin smoking and injecting situations,and in the meantime were exposed to herein simulacrum and apparatus after relaxation exercises.The neuroelectrophysiological reactions were mcagured with a multi-biofeedback instrument before and after the cue exposed.Self-reported craving was also assessed before and after cue exposed.Results The craving were increased[(18±22)mm vs.(29±29)mm,P＜0.01]after cue exposures compared to pre-exposure,EMG[(12±7)μN vs.(14±10)μV,P＜0.01]and SC[(6.8±4.3)μS vs.(7.4±4.3)μS,P＜0.01]also increased.But the percentages of δ,θ,α,SMR,low β,high β decreased compared to that under the cue exposures[8:(10.8±4.7)%vs.(9.7±4.4)%,P＜0.01;0:(6.8±2.0)%vs.(6.3±2.0)%,P＜0.01;α:(4.8±1.8)%vs.(4.5±1.7)%,P＜0.01;SMR:(3.0 ±1.2)%vs.(2.8±1.2)%,P＜0.01;low β:(2.6±1.1)%vs.(2.5±1.1)%,P＜0.01 and high β:(4.6 ±1.5)%vs.(4.5±1.5)%.P＜0.05].Conclusions The results indicate that drug-related cue induce heroin craving and electrophysiological reactions.     

Transcranial direct current stimulation of the frontal-parietal-temporal area attenuates cue-induced craving for heroin

BackgroundTranscranial direct current stimulation (tDCS) is an effective approach to modulate brain region functions. We assessed if a single tDCS session over the bilateral frontal-parietal-temporal (FPT) areas would reduce cue induced craving in heroin addicts.MethodsTwenty non-treated, long-term heroin-addicted subjects were randomly assigned to receive either real tDCS (1.5 mA, cathodal over bilateral FPT for 20 min) or control tDCS stimulation (turning off the stimulation after 30 s). The participants received heroin cue exposure (containing both injection and inhalation procedures) before and after stimulation and rated their craving after each block of cue presentation.ResultsStimulation of the bilateral FPT with real tDCS for 20 min reduced craving scores significantly (68 ± 8.4 pre-stimulation vs. 43 ± 7.6 post-stimulation, p = 0.003), while the control stimulation group showed no significant changes. No side effects of tDCS were reported.ConclusionsOne session of tDCS over bilateral FPT area significantly reduced subjective craving score induced by heroin cues in heroin addicted subjects.     

对海洛因依赖者心理健康与应对方式的研究

目的了解海洛因依赖者的心理健康状况及应对方式。方法对入组的60例吸毒者,在脱毒后、出所前、出所随访中作SCL-90和简易应对方式的测查,并与正常对照组比较分析。结果SCL-90和简易应对方式各因子均值比较,心理症状戒毒组比正常对照组高（P〈0.05）,积极应对戒毒组比正常对照组低（P〈0.05）,消极应对戒毒组比正常对照组高（P〈0.05）,消极应对与心理症状显著相关（P〈0.05）。出所前组与正常男性比较,仅其他因子（睡眠饮食障碍）戒毒者高（P〈0.05）。所外随访未复吸组与正常对照男性比较,无显著差异（P〉0.05）。回顾未复吸组在往所戒毒期间与正常对照男性比较,有躯体化、强迫、抑郁、焦虑、敌对、精神、其他7个因子和总均分有显著差异（P〈0.05）,17例复吸者作了同样的比较分析,除积极应对因子外,余因子均有显著差异（P〈0.05）。17例复吸者再入所时,各因子均值高于正常对照组（P〈0.05）。结论吸食海洛因成瘾可造成吸毒者心理健康状况恶化和应对方式不良,心理症状与消极应对方式相关,有诸多心理健康问题和对社会应激事件通常采用消极应对方式的戒毒者,其复吸的可能性要大。     

特麦角脲对大鼠海洛因自身给药的影响

目的 观察多巴胺D2受体部分激动剂--特麦角脲对大鼠海洛因固定比率、累进比率自身给药行为的影响.方法 对64只雄性SD大鼠分别处理如下:(1)取16只大鼠训练自身给水(自然奖赏模型对照),造模成功后随机分为2组,分别接受特麦角脲0.4 mg/kg和生理盐水腹腔注射干预,观察对大鼠固定比率自身给水行为的影响.(2)取32只大鼠训练海洛因固定比率自身给药,自身给药行为稳定后随机分为4组,每组8只,分别腹腔注射特麦角脲3种剂量(0.1,0.2,0.4 mg/kg体质量)和生理盐水(对照组),观察不同剂量特麦角脲对大鼠海洛因固定比率自身给药行为的影响.(3)取16只大鼠训练海洛因累进比率自身给药,造模成功后随机分为2组,分别接受特麦角脲0.4mg/kg和生理盐水腹腔注射干预,观察对大鼠海洛因累进比率自身给药行为的影响.结果 (1)特麦角脲0.4 mg/kg组固定比率自身给水行为与生理盐水干预组相比,差异无统计学意义(P>0.05).(2)特麦角脲0.2 mg/kg组和0.4 mg/kg组的大鼠海洛因固定比率自身给药次数干预前后的差值[(6.25±3.31)次和(11.75±4.92)次]高于生理盐水对照组[(-1.12±4.30)次],差异均有统计学意义(均P<0.01).(3)特麦角脲0.4 mg/kg组的大鼠累进比率自身给药的断点干预前后的差值[(20.2±8.7)次]高于生理盐水组[(-1.1±4.3)次],差异有统计学意义(P<0.01).结论 D2受体部分激动剂特麦角脲可降低海洛因固定比率和累进比率自身给药行为,以降低海洛因使用期的强化效应.     

Randomized controlled trial comparing the effectiveness and safety of intranasal and intramuscular naloxone for the treatment of suspected heroin overdose

Aims   Traditionally, the opiate antagonist naloxone has been administered parenterally; however, intranasal (i.n.) administration has the potential to reduce the risk of needlestick injury. This is important when working with populations known to have a high prevalence of blood-borne viruses. Preliminary research suggests that i.n. administration might be effective, but suboptimal naloxone solutions were used. This study compared the effectiveness of concentrated (2 mg/ml) i.n. naloxone to intramuscular (i.m.) naloxone for suspected opiate overdose.
Methods   This randomized controlled trial included patients treated for suspected opiate overdose in the pre-hospital setting. Patients received 2 mg of either i.n. or i.m. naloxone. The primary outcome was the proportion of patients who responded within 10 minutes of naloxone treatment. Secondary outcomes included time to adequate response and requirement for supplementary naloxone. Data were analysed using multivariate statistical techniques.
Results   A total of 172 patients were enrolled into the study. Median age was 29 years and 74% were male. Rates of response within 10 minutes were similar: i.n. naloxone (60/83, 72.3%) compared with i.m. naloxone (69/89, 77.5%) [difference: −5.2%, 95% confidence interval (CI) −18.2 to 7.7]. No difference was observed in mean response time (i.n.: 8.0, i.m.: 7.9 minutes; difference 0.1, 95% CI −1.3 to 1.5). Supplementary naloxone was administered to fewer patients who received i.m. naloxone (i.n.: 18.1%; i.m.: 4.5%) (difference: 13.6%, 95% CI 4.2–22.9).
Conclusions   Concentrated intranasal naloxone reversed heroin overdose successfully in 82% of patients. Time to adequate response was the same for both routes, suggesting that the i.n. route of administration is of similar effectiveness to the i.m. route as a first-line treatment for heroin overdose.     

Route of administration influences substitution patterns in rats trained to discriminate methadone vs. vehicle

Replacement therapy with the synthetic μ-opioid agonist methadone is an efficacious treatment for opioid abuse. While much is known about methadone's pharmacology, its discriminative stimulus properties remain largely unexplored. The present study sought to establish methadone discrimination in rats. Moreover, some research suggests that route of administration alters the discriminative stimulus of methadone. Thus, the present study also compared intraperitoneal (i.p.) and subcutaneous (s.c.) routes of administration. Male Sprague–Dawley rats were trained to discriminate 3.0 mg/kg methadone (i.p.) from vehicle in a two-lever discrimination procedure. Generalization tests were conducted with a variety of compounds administered i.p. and s.c. Methadone fully substituted for itself, yielding ED₅₀s of 1.5 mg/kg (i.p.) and 0.2 mg/kg (s.c.). Naltrexone (i.p.), an opioid antagonist produced a dose-dependent reduction in methadone-appropriate responding. The methadone stereoisomers fully substituted for methadone when given s.c.; however, when administered i.p., (+) and (−) methadone produced partial and no substitution, respectively. Heroin fully generalized to methadone regardless of administration route, while morphine fully substituted when given s.c., but not i.p. The kappa-agonist U50-488 failed to generalize to methadone with either route of administration. These results demonstrated that methadone's discriminative stimulus is mediated through μ-opioid receptor activity and is similar to that of commonly abused opioids (heroin, morphine). Additionally, route of administration produced differential results for many of the drugs tested, suggesting decreased drug bioavailability following i.p. administration due to hepatic first pass metabolism. Taken together, these results suggest that methadone's shared subjective effects with abused opioids, as well as its unique metabolic properties contribute to its efficacy in opioid maintenance therapy.     

海洛因依赖稽延性戒断症状的多因素回归分析

目的探讨海洛因依赖稽延性戒断症状的影响因素。方法以一般人口学资料、汉密顿焦虑量表(HAMA)、稽延性戒断症状评定量表(PWSRS)、症状自评量表(SCL-90)、人格诊断问卷(PDQ)、药物成瘾者生命质量量表(QOL-DA)、社会支持评定量表(SSRS)为评估工具,评估120例海洛因依赖者稽延性戒断症状的心理、社会因素;并测定去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)浓度,进行动态心电图24小时心率变异分析(HRV),评估生物学因素。结果海洛因依赖稽延性戒断症状主要受复吸、SCL-90躯体化、PDQ回避型、动态心电图RR间期的标准差(SDNN)、动态心电图低频功率与高频功率之比(LF/HF)、5-HT的影响,标准回归系数依次为:0.241、0.388、0.109、0.213、0.183、0.077。结论海洛因依赖者稽延性戒断症状受生物、心理、社会三方面的影响,因此治疗需采取综合治疗措施。     

海洛因依赖症患者肺结核发病状况调查

目的了解海洛因依赖症患者肺结核发病状况。方法回顾性分析30例接受美沙酮治疗的海洛因依赖症患者合并肺结核的胸片特点及治疗情况,并分析病因。结果海洛因依赖症患者肺结核的发病率比普通人群明显增高,而且病情重,有2处以上病灶9例（30%）、合并症多、病程长、复治率高（15.38%）。结论加强对这类患者的管理、随访和抗结核治疗,对患者的健康,对减少传染源,减少对社会的危害有着深远的意义。