An electromyographic method for the assessment of naloxone-induced abstinence in morphine-dependent rats

Summary The electromyographic (EMG) activities of suprahyoideal muscle were recorded to measure naloxone-precipitated abstinence signs in morphine-dependent rats anesthetized with urethane (1 g/kg). Rats were rendered dependent on morphine by implanting 2 morphine pellets (75 mg each) and abstinence signs were induced by intravenous injections of various doses of naloxone at different times after pellet implantation. Three precipitated abstinence signs, a) myoclonic twitch activity (MTA), b) mastication, and c) body shakes were observed on EMG recordings after the injection of naloxone. Of these symptoms, only the MTA induced by naloxone (10 g/kg) occurred 4 h after pellet implantation and its sensitivity to naloxone increased with prolonged pellet implantation. Both mastication and precipitated shakes could be induced at 24 h. However, higher doses of naloxone were required to produce the shakes than is required to induce mastication. There appears to be a positive correlation between the intensity of naloxone-induced MTA and the degree of physical dependence on morphine. Since the MTA and mastication can be induced by low doses of naloxone in morphine-dependent rats, we suggest that these two parameters may be used to detect morphine abstinence signs in this species.Deceased February 13, 1979     

Précipitation et prévention de l'abstinence chez le rat et la souris en état de dépendance aiguë. Comparaison de la naloxone,de la naltrexone et de la diprenorphine

Summary Abstinence signs were precipitated in rats by naloxone (1 mg·kg^-1 s.c.) injected at various times (from 1.5 to 16 h) after a single dose of morphine hydrochloride (15 or 50 mg·kg^-1 s.c.) administered incaqueous solution. Increasing the dose of morphine increased the latency of the phenomena and the duration of the underlying state shifts of signs as described by Bläsig et al. (1974) in chronically morphinized rats also occurred when increasing the dose of morphine and the time interval between the injections of morphine and of naloxone. Naltrexone and diprenorphine were also effective. These three antagonists, given before morphine, were able to prevent precipitated abstinence: however, naloxone was almost ineffective when the higher dose of morphine was used and when the time interval was long. In these latter conditions, naltrexone was definitely more effective and longer acting and diprenorphine still more so. The same characteristics were found for the protective action of the three antagonists in acutely morphinized mice and the same order for their potencies in precipitating abstinence in acutely morphinized mice. Like naloxone, naltrexone and diprenorphine facilitated a nociceptive reaction in normal mice.The abstinence signs precipitated in acutely morphinized rats or mice are probably not unmasked excitatory effects of morphine as such effects should have been increased rather than inhibited by previous administration of specific antagonists; they might correspond to potentiated effects of the antagonists themselves. The prevention by specific antagonists of the abstinence syndrome is most simply interpreted by antagonism (direct or indirect) of dependence induction, but other interpretations are not excluded.

     

呋喃唑酮厌恶疗法戒酒的临床观察及护理

目的：观察呋喃唑酮厌恶疗法戒酒的临床表现，探讨提高戒酒成功率的护理干预措施。方法：对23例酒依赖患者进行呋喃唑酮厌恶疗法，同时加强各阶段的护理干预。结果：一年随访戒酒成功率为87％。结论：患者有戒酒的愿望、家属的积极配合、全面的生活护理及适时的心理暗示是戒酒成功的重要条件。     

酒中毒患者戒酒相关因素的分析

目的：探讨酒中毒患者维持戒酒状态的相关因素。方法：30例住院的酒中毒病人(饮酒组)和13例出院以后戒酒二年以上的酒中毒病人(戒酒组)以明尼苏达多项个性调查表(MMPI)，汉密顿抑郁量表(HAMD)，汉密顿焦虑量表(HAMA)，以及有关酒中毒认识方面自编问卷，并调查入院记录及出院以后采取措施等进行对照研究。结果：饮酒组MMPI量表中L、Hs、D、Hy、Pt分高于戒酒组，Pd分饮酒组高于戒酒组，并出现1，2，4，6测图，HAMD，HAMA量表饮酒组高于戒酒组，说明有明显的躯体不适感和抑郁焦虑，强迫症特征和人格障碍特征，戒酒组对酒中毒认识分高于饮酒组，主动住院和出院以后坚持戒酒康复活动(简称AA活动)，戒酒组多高于饮酒组。结论：对酒中毒认识程度越深刻，戒酒效果越好，出院以后坚持AA活动是成功戒酒的有效措施。     

针刺对吗啡戒断大鼠脑组织一氧化氮合酶基因表达的影响

目的 :观察针刺对吗啡戒断大鼠脑组织神经元一氧化氮合酶基因 (nNOSmRNA)表达的影响 ,探讨针刺改善戒断症状的分子生物学机理。方法 :建立大鼠吗啡自然戒断模型 ,运用逆转录聚合酶链反应 (RT PCR)测定戒断大鼠脑组织nNOSmRNA的表达。观察戒断后 ,针刺“足三里”和一氧化氮合酶 (NOS)抑制剂L N 硝基精氨酸 (L NAME)对吗啡戒断大鼠戒断症状和脑组织nNOSmRNA表达的影响。结果 :戒断组nNOSmRNA表达增加 ,针刺组和L NAME组nNOSmRNA表达比戒断组减少。针刺组戒断积分比戒断组少 ,组间差异显著 (P <0 .0 1 )。结论 :针刺“足三里”穴具有抑制吗啡戒断大鼠脑组织nNOSmRNA表达的作用 ,提示这可能是针刺改善吗啡戒断症状的一个重要机制。     

Prevention of precipitated withdrawal symptoms by activating central cholinergic systems during a dependence-producing schedule of morphine in rats

Previous studies in this and other laboratories have suggested an important role for central cholinergic neurons in the expression of morphine withdrawal symptoms. This study was designed to determine whether the symptoms of withdrawal could be mitigated by normalization of the effect of morphine on cholinergic neurons. Since this effect is generally inhibitory, we used centrally acting cholinergic agonists to augment central cholinergic tone during chronic morphine infusion. Rats were made dependent following the intra-arterial (i.a.) infusion of increasing concentrations (35-100 mg kg(-1) day(-1)) of morphine over 5 days. I.a. injection of 0.5 mg/kg of naloxone precipitated a profound withdrawal response that included a dramatic increase in mean arterial pressure (MAP) which was maintained over the 60-min observation period, a short duration increase in heart rate (HR), and characteristic opiate withdrawal symptoms. In separate groups of rats, non-toxic doses (50 and 250 microg/kg) of the acetylcholinesterase (AChE) inhibitor, diisopropylflurophosphate (DFP) were administered as single daily injections concomitant with the morphine infusion. DFP treated rats, exhibited significantly reduced expression of the naloxone-evoked pressor response. The apparent anti-withdrawal effect of DFP was not reproduced by the selective peripherally acting AChE inhibitor, echothiophate, although both compounds effectively reduced the expression of certain other withdrawal symptoms. The centrally acting muscarinic cholinergic receptor agonist, arecoline, resulted in an even more impressive suppression of withdrawal symptoms. While not all symptoms associated with morphine withdrawal are mediated via central cholinergic pathways, these results suggest that physical dependence on morphine can be suppressed to a significant degree by the augmentation of central cholinergic activity during morphine administration.     

灵益胶囊联合美沙酮戒毒的疗效观察

目的:评价应用中西医结合对海洛因脱毒的疗效与不良反应.方法:对60例自愿戒毒者脱毒前期先给予美沙酮替代递减治疗,至末次口服20 mg·d-1后,分成A、B两组,A组30例在停美沙酮12小时后予以灵益胶囊口服治疗;B组30例继续给予美沙酮替代递减脱毒.结果:在控制戒断症状方面,在治疗早、中期,A组与B组相比无显著性差异(P＞0.05);治疗后期两组相比有非常显著性差异(P＜0.001);不良反应两组无显著性差异(P＞0.05).结论:美沙酮联合灵益胶囊脱毒治疗,临床疗效可靠,且有利于控制海洛因依赖者停用美沙酮后的稽留症状,副作用少,价格合理,值得推广使用.     

Serum and plasma brain-derived neurotrophic factor (BDNF) in abstinent alcoholics and social drinkers

Although the effects of alcohol on brain-derived neurotrophic factor (BDNF) have been extensively studied in rodents, BDNF levels have rarely been measured in abstinent, alcohol-dependent (AD) individuals. Interpretation of reported group comparisons of serum BDNF levels is difficult due to limited information regarding analytical variance, biological variability, and the relative contribution of platelet and plasma pools to serum BDNF. Analytical variance (intra- and inter-assay coefficients of variation) of the enzyme-linked immunosorbent assay (ELISA) was characterized. Within- and between-subject variability, and group differences in serum and plasma BDNF, was assessed on three separate days in 16, 4-week abstinent AD individuals (7M/9F) and 16 social drinkers (SDs; 8M/8F). Significantly higher mean (±sd) serum BDNF levels were observed for the AD group compared to the SD (p = 0.003). No significant difference in mean baseline plasma BDNF levels was observed between AD and SD groups. The low analytical variance, high day-to-day within-individual stability and the high degree of individuality demonstrates the potential clinical utility of measuring serum BDNF levels. The low correlations that we observed between plasma and serum levels are congruent with their representing separate pools of BDNF. The observation of higher basal serum BDNF in the AD group without a concomitant elevation in plasma BDNF levels indicates that the elevated serum BDNF in AD patients is not due to greater BDNF exposure. Further research is warranted to fully elucidate mechanisms underlying this alteration and determine the utility of serum BDNF as a predictor or surrogate marker of chronic alcohol abuse.