Craving-induced effects of different drug cues on persons abstaining from heroin

Background: The key factors of inducing drug cravings in persons abstaining from drug use remain a focus of addictions research. Given the accumulating evidences, the scope of cues investigated in the cue-reactivity paradigm has increased considerably. Yet, few studies have examined the effects of the intensity and endurance of different types of cues on their ability to induce craving. This study investigated differences among drug-cue words, negative physiological-cue words, and negative social-cue words in the induction of drug cravings among persons abstaining from heroin.

Methods: The sample consisted of 149 male abstinent heroin abusers from four addiction rehabilitation centers in China. Based on their abstinence lengths, they were labeled as short-term, medium-term, and long-term abstainer participants respectively. All participants completed a stress-imagery task and rated craving by visual analog scale.

Results: There was a significant interaction of cue type and abstinence length. There was no difference on the craving induced by three types of cue words in the short-term group. In the medium-term group, craving induced by negative social-cue words was significantly stronger than that by negative physiological-cue words, but not that by drug-cue words. In the long-term group, the craving induced by negative social-cue words remained the strongest, significantly stronger than that by both drug-cue words and negative physiological-cue words.

Conclusion: Negative social-cue words presented in the current study retain the ability to induce craving in heroin abstainers; this finding suggests that negative social cues encountered under more general circumstances could be a risk factor for relapse.     

吗啡依赖和戒断对大鼠杏仁核神经甾体和氨基酸递质水平的影响

目的研究吗啡依赖和戒断时大鼠杏仁核中神经甾体和氨基酸递质水平的变化。方法连续7天给予大鼠盐酸吗啡建立吗啡依赖模型。使用纳洛酮(2mg/kg)催促戒断,观察戒断症状并进行评分。将大鼠断头处死后,剥离大脑并分离出杏仁核,用液-液萃取和固相萃取法提取游离型和结合型神经甾体。神经甾体(包括脱氢表雄酮、孕烯醇酮、别孕烯醇酮、脱氢表雄酮硫酸酯和孕烯醇酮硫酸酯)的含量使用高效液相色谱-质谱法测定。甘氨酸、谷氨酸和γ-氨基丁酸的含量采用柱前OPA衍生-电化学检测-高效液相色谱法测定。结果与盐水对照组相比,吗啡依赖大鼠杏仁核中的脱氢表雄酮水平降低33 %(P<0·01)。与戒断对照组比较,吗啡戒断大鼠杏仁核中的孕烯醇酮和别孕烯醇酮水平分别升高45 %和42 %(P<0·05) ,γ-氨基丁酸水平降低18 %(P<0·01)。与吗啡依赖组比较,吗啡戒断组大鼠杏仁核中的孕烯醇酮和孕烯醇酮硫酸酯水平分别升高60 %和40 %(P<0·05) ,甘氨酸水平降低14 %(P<0·05)。结论吗啡依赖大鼠杏仁核中的脱氢表雄酮可能参与吗啡依赖的形成而与吗啡戒断症状的表达无关。其他神经甾体(包括孕烯醇酮、别孕烯醇酮和孕烯醇酮硫酸酯)则可能参与吗啡的戒断而与依赖的形成无关。纳洛酮催促戒断时,大鼠杏仁核中抑制性氨基酸递质的合成和释放受到抑制。表明大鼠杏仁核中的各种神经甾体和氨基酸递质在吗啡依赖和戒断时发生了不同的变化。     

Wound Botulism Associated with Black Tar Heroin

The incidence of wound botulism is increasing and the epidemiology of the disease is changing. The majority of new cases are associated with injection drug use, in particular, the use of Mexican black tar heroin. This case report and discussion of wound botulism illustrate the following important points: Dysphagia, dysphonia, diplopia, and descending paralysis, in association with injection drug use, should alert the treating physician to the possibility of wound botulism. In such patients, the onset of respiratory failure may be sudden and without clinically obvious signs of respiratory weakness. For the reported patient, maximum inspiratory force measurements were the only reliable indicator of respiratory muscle weakness. This is a measurement not routinely performed in the ED, but may prove essential for patients with suspected wound botulism. To minimize the effect of the botulinum toxin and to decrease length of hospital stay, antitoxin administration and surgical wound debridement should be performed early.     

血红素抑制内皮细胞损伤的形态学观察

目的 探讨血红素对人脐静脉内皮细胞氧化应激损伤的保护作用。方法 将培养的人脐静脉内皮细胞进行分组：对照组、损伤组、血红素组。观察各组细胞在光、电镜下形态学的改变。结果 在光镜下，血红素组细胞的生长状态明显优于损伤组；在电镜下，损伤组细胞核固缩，而血红素组细胞核幼稚，核仁明显。结论 在人脐静脉内皮细胞中，血红素对过氧化氢所造成的氧化应激损伤有明显的保护作用。     

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。     

Personality traits of agreeableness and extraversion are associated with ADH4 variation.

BACKGROUND: Personality traits are associated with substance dependence (SD); genetic factors may influence both. Strong associations between ADH4 variation and SD have been reported. We aimed to investigate the relationship between ADH4 variation and personality traits in the present study. METHODS: We assessed dimensions of the five-factor model of personality in 243 subjects with SD (175 European Americans [EAs] and 68 African Americans [AAs]) and 296 healthy control subjects (256 EAs and 40 AAs). We also genotyped 7 ADH4 markers (spanning the locus) and 38 unlinked ancestry-informative markers in these subjects. The relationships between the diplotypes, alleles, and genotypes at ADH4 and personality traits were examined using multivariate analysis of covariance (MANCOVA), controlling for potential confounders. RESULTS: Generally, SD patients, older individuals, and male subjects scored higher on neuroticism and lower on other personality factors. Personality factors were associated with the diplotypes. The allele A or genotype A/A of single nucleotide polymorphism (SNP)6 (rs1800759 at the gene promoter) was significantly associated with agreeableness scores. There were associations between extraversion and SNP1 (hcv2033010 at the 3' end) and SNP2 (rs1042364 in exon 9) in subjects with higher conscientiousness scores. CONCLUSIONS: The personality traits of agreeableness and extraversion are related to ADH4 polymorphism. Among the ADH4 markers that appear to predispose to certain personality traits, the functional variant rs1800759 (SNP6) in the promoter region is most important. We conclude that personality traits and SD have a partially overlapping genetic basis.     

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