Methamphetamine abuse and impairment of social functioning: A review of the underlying neurophysiological causes and behavioral implications.

The highly addictive drug methamphetamine has been associated with impairments in social cognitions as evidenced by changes in users' behaviors. Physiological changes in brain structure and functioning, particularly in the frontal lobe, have also been identified. The authors propose a biopsychosocial approach to understanding the effects of methamphetamine addiction by relating the physiological effects of the drug to the behaviors and social cognitions of its users, through the application of the theory of mind paradigm. Although onset of methamphetamine use has been linked to the desire for socialization, chronic use has been associated with an increase in depression, aggressiveness, and social isolation, behaviors that also implicate involvement of the frontal lobe. The reviewed literature provides strong circumstantial evidence that social-cognitive functioning is significantly impacted by methamphetamine use and that the social isolation, depression, and aggressiveness associated with chronic use is due to more than just the social withdrawal associated with addiction. Treatment considerations for methamphetamine must therefore consider the role of social cognition, and pharmacological responses must address the documented impact of the drug on frontal lobe functioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Many Drugs of Abuse May Be Acutely Transformed to Dopamine,Norepinephrine and Epinephrine In Vivo

It is well established that a wide range of drugs of abuse acutely boost the signaling of the sympathetic nervous system and the hypothalamic–pituitary–adrenal (HPA) axis, where norepinephrine and epinephrine are major output molecules. This stimulatory effect is accompanied by such symptoms as elevated heart rate and blood pressure, more rapid breathing, increased body temperature and sweating, and pupillary dilation, as well as the intoxicating or euphoric subjective properties of the drug. While many drugs of abuse are thought to achieve their intoxicating effects by modulating the monoaminergic neurotransmitter systems (i.e., serotonin, norepinephrine, dopamine) by binding to these receptors or otherwise affecting their synaptic signaling, this paper puts forth the hypothesis that many of these drugs are actually acutely converted to catecholamines (dopamine, norepinephrine, epinephrine) in vivo, in addition to transformation to their known metabolites. In this manner, a range of stimulants, opioids, and psychedelics (as well as alcohol) may partially achieve their intoxicating properties, as well as side effects, due to this putative transformation to catecholamines. If this hypothesis is correct, it would alter our understanding of the basic biosynthetic pathways for generating these important signaling molecules, while also modifying our view of the neural substrates underlying substance abuse and dependence, including psychological stress-induced relapse. Importantly, there is a direct way to test the overarching hypothesis: administer (either centrally or peripherally) stable isotope versions of these drugs to model organisms such as rodents (or even to humans) and then use liquid chromatography-mass spectrometry to determine if the labeled drug is converted to labeled catecholamines in brain, blood plasma, or urine samples.     

Comparative subjective effects of seven drugs including lysergic acid diethylamide (LSD-25).

"Five Ss were tested on nine occasions under two placebos of tap water and under an average effective dose of 7 drugs—ergometerine (Ergonovine), ethyl alcohol, scopolamine (hyroscine), d-1-brom lysergic acid diethylamide (BOL-148), methamphetamine hydrochloride (Methedrine or Pervitin), lysergic acid monoethylamide (LAE-32), and lysergic acid diethylamide (LSD-25) during 9 different experimental sessions… . The Ss completed a questionnaire inquiring about their perceptual, physiological and cognitive state before they received the drug or placebo and .5, 2.5 and 4.5 hours after receiving it… . Although differentiation between 3 lysergic acid derivatives, Ergonovine, LAE-32, and BOL-148, and between alcohol, methamphetamine, and scopolamine was not clear cut, the number of responses to the questionnaire under these drugs was clearly greater than those given under water… . LSD-25 clearly produced the most frequent and the largest positive responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

气相色谱-红外光谱联用法快速鉴定毒品种类及其纯度

建立了气相色谱-红外光谱(GC-FTIR)联用技术快速鉴别毒品种类和分析毒品纯度的方法,具有操作简单、分析快和准确性高等优点,适合于鉴别未知毒品。利用红外光谱特征吸收峰和色谱相对保留时间鉴别毒品种类,毒品浓度(y)与其色谱峰相对面积(x)在0.05~1.00 mg/L范围内呈现良好的线性关系,据此确定毒品纯度。本方法用于实际案例分析取得了满意的结果。     

甲基苯丙胺滥用与依赖的相关影像学研究进展

长期滥用甲基苯丙胺（methamphetamine, MA）可引起患者脑内血流灌注、葡萄糖代谢、某些生物化学物质甚至局部脑结构的改变。本文主要对MA滥用与依赖引起的脑结构及功能改变的影像学表现进行综述,以了解MA滥用与依赖者脑结构及功能的改变与其认知和动机功能损害之间的关系。主要总结利用单光子发射计算机断层成像术 计算机断层扫描术（single-photon emission computed tomography computed tomography, SPECT-CT）、正电子发射断层成像术-计算机断层扫描仪（positron emission tomography-computed tomography, PET-CT）、磁共振成像（magnetic resonance imaging, MRI）、功能性磁共振成像（functional magnetic resonance imaging, fMRI）、质子磁共振波谱（proton magnetic resonance spectroscopy, proton MRS）影像技术观察MA滥用与依赖引起的脑解剖结构改变,以及在生理状态下观察脑内血流灌注及葡萄糖代谢的变化,研究参与甲基苯丙胺依赖的脑区、核团,并且MRS能够检测出脑内某些神经化学物质的变化。在临床工作中联合应用影像检查技术,能够监测MA滥用与依赖期间大脑的变化及预测复吸的可能性,对临床医师的治疗决策起重要作用。     

基于光诱导延迟发光的微量毒品检测研究

基于单光子计数测量原理,设计并构建了基于光 诱导延迟发光的微量毒品检测系统。对检测系统的性 能进行了评测,结果显示,光电倍增管(PMT)的固有暗计数为11.5±0.7 photon/s,系统 暗计数为11.7±0.7 photon/s,对外界杂散光的屏蔽性能优异。利用本系统检测得到了健 康人和涉嫌吸食冰毒人员的血 清样本的延迟发光衰减曲线和参数值,结果表明,两种样本的各个参数值差异非常明显 。本检测系统灵敏 度高,所需样品量少,检测过程不与样品直接接触,为生物样本中微量毒品的检测提供了强 有力的工具。     

Inactivation of the Lateral Hypothalamus Attenuates Methamphetamine-Induced Conditioned Place Preference through Regulation of Kcnq3 Expression

Repeated administration of methylamphetamine (MA) induces MA addiction, which is featured by awfully unpleasant physical and emotional experiences after drug use is terminated. Neurophysiological studies show that the lateral hypothalamus (LH) is involved in reward development and addictive behaviors. Here, we show that repeated administration of MA activates the expression of c-Fos in LH neurons responding to conditioned place preference (CPP). Chemogenetic inhibition of the LH can disrupt the addiction behavior, demonstrating that the LH plays an important role in MA-induced reward processing. Critically, MA remodels the neurons of LH synaptic plasticity, increases intracellular calcium level, and enhances spontaneous current and evoked potentials of neurons compared to the saline group. Furthermore, overexpression of the potassium voltage-gated channel subfamily Q member 3 (Kcnq3) expression can reverse the CPP score and alleviate the occurrence of addictive behaviors. Together, these results unravel a new neurobiological mechanism underlying the MA-induced addiction in the lateral hypothalamus, which could pave the way toward new and effective interventions for this addiction disease.     

Selective Inhibition of PDE4B Reduces Methamphetamine Reinforcement in Two C57BL/6 Substrains

Methamphetamine (MA) is a highly addictive psychostimulant drug, and the number of MA-related overdose deaths has reached epidemic proportions. Repeated MA exposure induces a robust and persistent neuroinflammatory response, and the evidence supports the potential utility of targeting neuroimmune function using non-selective phosphodiesterase 4 (PDE4) inhibitors as a therapeutic strategy for attenuating addiction-related behavior. Off-target, emetic effects associated with non-selective PDE4 blockade led to the development of isozyme-selective inhibitors, of which the PDE4B-selective inhibitor A33 was demonstrated recently to reduce binge drinking in two genetically related C57BL/6 (B6) substrains (C57BL/6NJ (B6NJ) and C57BL/6J (B6J)) that differ in their innate neuroimmune response. Herein, we determined the efficacy of A33 for reducing MA self-administration and MA-seeking behavior in these two B6 substrains. Female and male mice of both substrains were first trained to nose poke for a 100 mg/L MA solution followed by a characterization of the dose–response function for oral MA reinforcement (20 mg/L–3.2 g/L), the demand-response function for 400 mg/L MA, and cue-elicited MA seeking following a period of forced abstinence. During this substrain comparison of MA self-administration, we also determined the dose–response function for A33 pretreatment (0–1 mg/kg) on the maintenance of MA self-administration and cue-elicited MA seeking. Relative to B6NJ mice, B6J mice earned fewer reinforcers, consumed less MA, and took longer to reach acquisition criterion with males of both substrains exhibiting some signs of lower MA reinforcement than their female counterparts during the acquisition phase of the study. A33 pretreatment reduced MA reinforcement at all doses tested. These findings provide the first evidence that pretreatment with a selective PDE4B inhibitor effectively reduces MA self-administration in both male and female mice of two genetically distinct substrains but does not impact cue-elicited MA seeking following abstinence. If relevant to humans, these results posit the potential clinical utility of A33 or other selective PDE4B inhibitors for curbing active drug-taking in MA use disorder.     

Sex-Specific Alterations in Dopamine Metabolism in the Brain after Methamphetamine Self-Administration

Methamphetamine (METH) use disorder affects both sexes, with sex differences occurring in behavioral, structural, and biochemical consequences. The molecular mechanisms underlying these differences are unclear. Herein, we used a rat model to identify potential sex differences in the effects of METH on brain dopaminergic systems. Rats were trained to self-administer METH for 20 days, and a cue-induced drug-seeking test was performed on withdrawal days 3 and 30. Dopamine and its metabolites were measured in the prefrontal cortex (PFC), nucleus accumbens (NAc), dorsal striatum (dSTR), and hippocampus (HIP). Irrespective of conditions, in comparison to females, male rats showed increased 3,4-dihydroxyphenylalanine (DOPA) in the PFC, dSTR, and HIP; increased cys-dopamine in NAc; and increased 3,4-dihydroxyphenylethanol (DOPET) and 3,4-dihydroxyphenylacetic acid (DOPAC) in dSTR. Males also showed METH-associated decreases in DA levels in the HIP but increases in the NAc. Female rats showed METH-associated decreases in DA, DOPAL, and DOPAC levels in the PFC but increases in DOPET and DOPAC levels in the HIP. Both sexes showed METH-associated decreases in NAc DA metabolites. Together, these data document sex differences in METH SA-induced changes in DA metabolism. These observations provide further support for using sex as an essential variable when discussing therapeutic approaches against METH use disorder in humans.     

利用拉曼光谱法检测饮料中的甲基苯丙胺

利用拉曼光谱技术建立了快速检测饮料中甲基苯丙胺的方法.对市场出售的可乐、脉动、橙汁三种饮料进行甲基苯丙胺不同加标浓度的表面增强拉曼光谱检测,结果表明加标饮料的拉曼光谱对比未加标饮料出现了明显的变化,在991 cm-1、1016 cm-1,1201 cm-1处出现了强烈的拉曼信号,这些特征稳定存在,可以作为鉴定此3种饮料...