A General Role for Early Onset Cues and Intra-Event Learning; Comment on McDonald and Siegel (2004).

Research on classical conditioning with drug unconditional stimuli has had a profound effect on the understanding of general conditioning processes. The experiment reported by R. V. McDonald and S. Siegel (see record 2004-10475-001) demonstrates that cues coincident with the onset of an event can become associated with the rest of the event. This sort of learning is probably ubiquitous and has been proposed as a mechanism behind the development of panic disorder, in which interoceptive cues coincident with the start of a panic attack can be associated with the rest of the attack and can eventually come to elicit full-blown panic on their own. Evidence that extinction exposure to early onset cues can reduce their power is especially important. Drug conditioning research continues to provide a powerful testing ground for important general principles of learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Drug Onset Cues, Conditioned Withdrawal, and Drug Relapse: Comment on McDonald and Siegel (2004).

Previous research has shown that under certain conditions environmental cues associated with morphine administration induce drug-opposite conditioned effects that mimic symptoms of opiate withdrawal. R. V. McDonald and S. Siegel (see record 2004-10475-001) extend these observations by demonstrating that acute exposure to a low dose of morphine induces symptoms of opiate withdrawal in rats previously exposed to a high dose of morphine. They hypothesized that early drug onset cues, repeatedly paired with later, larger drug effects, mediate the paradoxical effect of the low drug dose on behavior. They also hypothesized that conditioned withdrawal symptoms induced by the early drug onset cues may mediate the "priming" effect of drugs on relapse and craving. The authors of this comment discuss the degree to which the literature supports this hypothesis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disentangling the Sources of Opioid Withdrawal Responses: Comment on McDonald and Siegel (2004).

R. V. McDonald and S. Siegel (see record 2004-10475-001) present new evidence for the idea that opioid drug-opposite responses can become conditioned to cues of initial drug onset and that they could, therefore, play a role in the development of tolerance of some drug effects and a role in the elicitation of withdrawal-like symptoms in cases in which addicted individuals are exposed to small doses of the drug they normally consume. In this comment, some puzzling features of the data are discussed, and alternative explanations are suggested. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fentanyl but Not Morphine or Buprenorphine Improves the Severity of Necrotizing Acute Pancreatitis in Rats

Opioids are widely used for the pain management of acute pancreatitis (AP), but their impact on disease progression is unclear. Therefore, our aim was to study the effects of clinically relevant opioids on the severity of experimental AP. Various doses of fentanyl, morphine, or buprenorphine were administered as pre- and/or post-treatments in rats. Necrotizing AP was induced by the intraperitoneal injection of L-ornithine-HCl or intra-ductal injection of Na-taurocholate, while intraperitoneal caerulein administration caused edematous AP. Disease severity was determined by laboratory and histological measurements. Mu opioid receptor (MOR) expression and function was assessed in control and AP animals. MOR was expressed in both the pancreas and brain. The pancreatic expression and function of MOR were reduced in AP. Fentanyl post-treatment reduced necrotizing AP severity, whereas pre-treatment exacerbated it. Fentanyl did not affect the outcome of edematous AP. Morphine decreased vacuolization in edematous AP, while buprenorphine pre-treatment increased pancreatic edema during AP. The overall effects of morphine on disease severity were negligible. In conclusion, the type, dosing, administration route, and timing of opioid treatment can influence the effects of opioids on AP severity. Fentanyl post-treatment proved to be beneficial in AP. Clinical studies are needed to determine which opioids are best in AP.     

超高效液相-串联质谱法测定食品中罂粟壳成分

目的 建立超高效液相-串联质谱法测定食品中罂粟壳成分的分析方法。方法 罂粟壳经乙腈提取后, 经PCX固相萃取柱净化, 选择BEH HILIC柱(粒径1.7 μm, 2.1 mm×100 mm), 以含0.1%甲酸的10 mmol/L乙酸铵溶液和甲酸乙腈溶液(0.1%)作为流动相进行梯度洗脱, 在0.3 mL/min流速下, 以多反应监测(multiple reaction monitoring, MRM)扫描模式进行检测, 外标法定量。结果 吗啡、可待因在25~250 μg/kg添加浓度范围内, 回收率为68.30~80.81%。罂粟碱、那可丁、蒂巴因在0.5~2.5 μg/kg添加浓度范围内, 回收率为68.34%~78.91%。本方法罂粟碱、那可丁、蒂巴因、吗啡和可待因定量限分别为0.5、0.5、0.5、25、25 μg/kg。结论 该方法简便、快速、可靠, 可用于各种食品中罂粟壳生物碱的快速筛查与确证。     

Narp regulates long-term aversive effects of morphine withdrawal.

Although long-lasting effects of drug withdrawal are thought to play a key role in motivating continued drug use, the mechanisms mediating this type of drug-induced plasticity are unclear. Because Narp is an immediate early gene product that is secreted at synaptic sites and binds to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, it has been implicated in mediating enduring forms of synaptic plasticity. In previous studies, the authors found that Narp is selectively induced by morphine withdrawal in the extended amygdala, a group of limbic nuclei that mediate aversive behavioral responses. Accordingly, in this study, the authors evaluate whether long-term aversive effects of morphine withdrawal are altered in Narp knockout (KO) mice. The authors found that acute physical signs of morphine withdrawal are unaffected by Narp deletion. However, Narp KO mice acquire and sustain more aversive responses to the environment conditioned with morphine withdrawal than do wild type (WT) controls. Paradoxically, Narp KO mice undergo accelerated extinction of this heightened aversive response. Taken together, these studies suggest that Narp modulates both acquisition and extinction of aversive responses to morphine withdrawal and, therefore, may regulate plasticity processes underlying drug addiction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

吗啡对 SH-SY5Y 细胞中 HSP70蛋白的调控作用

目的：观察吗啡对人神经母细胞瘤（SH-SY5Y）细胞中热休克蛋白70（HSP70）的调控作用。方法将维甲酸诱导分化的 SH-SY5Y 细胞随机分为4组：正常对照组（Con 组）,给予 PBS 作用48 h;吗啡组（Mor 组）,给予吗啡10μmol 作用48 h;吗啡＋纳络酮组（Mor＋Nal 组）,给予纳洛酮100μmol 作用30 min,之后给予吗啡10μmol 作用48 h;纳络酮组（Nal 组）,给予纳洛酮100μmol 作用48 h。采用免疫印迹方法检测各组 HSP70蛋白表达水平。结果与 Con 组比较,Mor 组 SH-SY5Y 细胞中 HSP70蛋白表达水平显著升高（P ＜0．001）;与 Mor 组比较,Mor＋Nal 组、Nal 组 SH-SY5Y 细胞中 HSP70蛋白表达水平均明显抑制（P ＜0．01或 P ＜0．001）。结论吗啡对 HSP70蛋白表达具有促进作用。     

Revisiting Anna O.: A case of chemical dependence.

The famous clinical case of Anna O./Bertha Pappenheim, who was treated by Breuer from 1880 to 1882 and whose pathology was discussed by him and Freud in an 1895 article (J. Breuer & S. Freud, 1895/1955), is reviewed based on biographical information regarding the patient, which appeared from 1953 onward. The objective of this article is to show that, in order to better understand the case, the diagnosis of chloral hydrate and morphine dependence, as well as that of mood disorder (primary or drug induced), has to be taken into account. The method used is a careful literature review. The conclusion is that, based on all available data disclosed in recent years, these 3 diagnoses should be considered in this case, which is the most studied one in the history of psychoanalysis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

盐酸羟考酮用于腹腔镜直肠癌根治术患者镇痛效果的观察

目的: 探讨盐酸羟考酮注射液对腹腔镜直肠癌根治术患者自控镇痛时的效价和副作用,并与吗啡自控镇痛进行比较。方法: 择期行腹腔镜直肠癌根治术患者120例,ASAⅠ~Ⅲ级,按照随机数字表法分成羟考酮组(O组)和吗啡组(M组),每组各60例。手术结束前15 min两组分别给予镇痛负荷量,然后接病人自控镇痛泵。手术结束后观察两组视觉模拟评分、镇痛药物用量、不良反应、镇静水平和患者满意度。结果: 两组观察时间内静息和运动时VAS评分无显著差异(P﹥0.05),O组镇痛后 4 h(2.3±0.8)、8 h(2.5±0.7)和 12 h (3.1±0.8) Ramsay评分显著低于M组(3.8±0.5, 3.9±0.7, 4.0±0.5)(P﹤0.01,P﹤0.05)。O组 48 h 累计呕吐发生率(11%)低于M组(20%)(P﹤0.05),呼吸抑制发生率低于M组(P﹤0.01)。两组间患者镇痛满意度无统计学差异(P﹥0.05)。结论: 盐酸羟考酮可有效用于腹腔镜直肠癌根治术自控镇痛,且呼吸抑制和呕吐发生率低,镇痛效果与吗啡相当。     

The role of cholecystokinin in conditional compensatory responding and morphine tolerance in rats.

As elaborated in the conditioning analysis of tolerance, cues present at the time of drug administration become associated with the drug effect. A particularly salient cue that may become associated with the drug effect is the pharmacological drug-onset cue inherent to drug administration. Drug-associated cues contribute to tolerance by eliciting a conditional compensatory response that attenuates the drug effect. For example, the early drug effect, having been paired with the subsequent larger drug effect, may elicit the release of antiopioid peptides that counter opioid effects. The role of a putative antiopioid peptide, cholecystokinin-8 (CCK), in the associative mechanisms of opiate tolerance was evaluated. The results of these experiments suggest that a CCK2 receptor antagonist attenuates both the expression of opiate tolerance and the conditional compensatory response hypothesized to mediate such tolerance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)