分子印迹固相萃取-高效液相色谱法测定尿液中甲基苯丙胺和苯丙胺

目的:建立快速、准确的尿液中甲基苯丙胺(MA)及其代谢产物苯丙胺(AMP)的分子印迹固相萃取(MISPE)高效液相色谱测定方法。方法:尿液与10 mmol/L醋酸铵缓冲液(pH 8.0)混合后离心分离(8000 rpm),采用预先活化过的分子印迹固相萃取柱净化,以醋酸/乙腈溶液洗脱,在XBridge RP18色谱柱上,以甲醇-乙腈-水溶液(15∶30∶55,V/V/V)为流动相,采用210 nm波长进行检测。结果:MA和AMP的加标回收率在88.5%～97.0%范围,其相对标准偏差均小于5.0%,在0.05 mg/L～15.0 mg/L范围呈现良好的线性,其回归系数大于0.999,检出限(LODs)分别为0.005 mg/L和0.01 mg/L。结论:本方法回收率高,净化效果显著,稳定性好,杂质干扰少,可满足临床吸毒病人尿液中MA和AMP的检测要求。     

Methamphetamine use and sexual risks for HIV infection in Cape Town,South Africa

Aims: The current study examined the use of methamphetamine (Meth) in relation to HIV risks in a South African community sample.

Design and setting: Street intercept methods were used to collect surveys of substance use and sexual behavior from 441 men and 521 women living in a racially mixed township in Cape Town South Africa.

Findings: Results showed that 78 (18%) men and 63 (12%) women had used Meth, and 49 (11%) men and 34 (6%) women ever had used Meth in the preceding 6 months. Other than alcohol, cannabis was the most commonly used drug followed by Meth. We found that Meth use was closely associated with other drug use, indicating a pattern of poly‐substance use among Meth users. Recent Meth use was associated with being male, engaging in unprotected intercourse and having multiple sex partners in the previous 6 months. Meth users also demonstrated greater condom use than non‐users, although less than half of all intercourse occasions among Meth users were condom protected.

Conclusions: Meth is used by a substantial number of people in one area of South Africa and the close association of Meth and sexual risk practices raises concern that Meth could fuel the spread of HIV infection in new South African sub‐populations.     

The effects of carbamazepine on two animal models of depression

Some clinical reports on antimanic, antidepressant and prophylactic effects of carbamazepine (CBZ) in manic-depressive illness have appeared since its initial use as an anticonvulsant drug. The present report deals with the effects of CBZ on two animal models of depression, namely the potentiation of amphetamine-induced anorexia, and the behavioral despair model. Carbamazepine (10, 20 or 40 mg/kg) neither modified the methamphetamine anorectic effect, nor induced anorexia when administered alone. Subacute and chronic administration of imipramine (4 or 15 mg/kg) decreased immobility of rats in the behavioral despair model. Subacute and chronic administration of CBZ (40 mg/kg) also decreased immobility, whereas the dose of 10 mg/kg CBZ was effective only after chronic treatment. It was concluded that CBZ is similar to atypical anti-depressants, since it did not potentiate the amphetamine-induced behavioral effect, but did have an effect on the behavioral despair model of depression.     

Methamphetamine causes lipid peroxidation and an increase in superoxide dismutase activity in the rat striatum

The administration of methamphetamine to experimental animals results in damage to nigrostriatal dopaminergic neurons. In the present study, we demonstrated that both the acute repeated and the chronic administration of methamphetamine causes an increase in thiobarbituric acid reactive substances, which are indicators of lipid peroxidation, and superoxide dismutase activity in the rat striatum. The results of present study strengthen the notion that reactive oxygen species may play an important role in the methamphetamine-induced neurotoxicity.     

Enlarged striatum in abstinent methamphetamine abusers: a possible compensatory response.

BACKGROUND: Little is known about structural brain abnormalities associated with methamphetamine (METH) abuse; therefore, we aimed: 1) to evaluate possible morphometric changes, especially in the striatum of recently abstinent METH-dependent subjects; 2) to evaluate whether morphometric changes are related to cognitive performance; and 3) to determine whether there are sex-by-METH interactions on morphometry. METHODS: Structural MRI was performed in 50 METH and 50 comparison subjects with the same age range and sex proportion; quantitative morphometric analyses were performed in the subcortical gray matter, cerebellum and corpus callosum. Neuropsychological tests were also performed in 44 METH and 28 comparison subjects. RESULTS: METH users showed enlarged putamen (left: + 10.3%, p = .0007; right: + 9.6%, p = .001) and globus pallidus (left: + 9.3%, p = .002; right: + 6.6%, p = .01). Female METH subjects additionally showed larger mid-posterior corpus callosum (+ 9.7%, p = .05). Although METH users had normal cognitive function, those with smaller striatal structures had poorer cognitive performance and greater cumulative METH usage. CONCLUSIONS: Since METH subjects with larger striatal structures had relatively normal cognitive performance and lesser cumulative METH usage, the enlarged putamen and globus pallidus might represent a compensatory response to maintain function. Possible mechanisms for the striatal enlargement include glial activation and inflammatory changes associated with METH-induced injury.     

Effects of repeated ritanserin on middle-aged poor sleepers

The present study was designed to investigate the effect of U-50, 488H, a highly selective kappa opioid agonist, on ipsilateral and contralateral circling behavior induced by methamphetamine and by apomorphine, respectively. U-50, 488H (3.2–10 mg/kg IP) by itself failed to induce either ipsilateral or contralateral circling in rats with unilateral nigral lesions produced by an injection of 6-hydroxydopamine. U-50, 488H produced a significant dosedependent inhibition of methamphetamine (1.0 mg/kg SC)elicited ipsilateral circling. However, it had no effect on contralateral circling induced by apomorphine (0.5 mg/kg SC). The present results indicate that U-50, 488H presynaptically inhibits the release of dopamine in the rat striatum.     

5,6-dihydroxytryptamine, a serotonergic neutotoxin, is formed endogenously in the rat brain

Methamphetamine (MA) in high doses produces long-term toxic effects on the serotonergic system in the rat brain, including depletions of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid and reductions in 5-HT reuptake and tryptophan hydroxylase activity. In this study, the formation of 5, 6-dihydroxytryptamine (5, 6-DHT), a serotonergic neurotoxin, was observed in the rat hippocampus after a single 100 mg/kg injection of MA. The 5, 6-DHT was detected by reverse-phase high-performance liquid chromatography with electrochemical detection in tissue samples taken 0.5-4 h after MA administration; the highest levels of 5, 6-DHT (0.032 ng/mg wet tissue) were detected at 1 h. Following administration of MA, 5-HT was also depleted in the neocortex, but 5, 6-DHT was not detected as frequently in this brain region as in the hippocampus. Comparisons were made between the long-term hippocampal 5-HT depletions seen either after an injection of MA or after intraventricular 5, 6-DHT infusions and the levels of 5, 6-DHT measured in the hippocampus shortly after each treatment. The amount of 5, 6-DHT produced after MA administration appears to be adequate to cause the observed long-term 5-HT depletions. We suggest that 5, 6-DHT formed from 5-HT may mediate the neurotoxic effects of MA on serotonergic nerve terminals.     

Effects of nimodipine on the amphetamine- and methamphetamine-induced decrease in tryptophan hydroxylase activity

The effects of nimodipine on the amphetamine- and methamphetamine-induced decrease in central tryptophan hydroxylase activity was examined. Rats were administered 4 or 5 injections of amphetamine or methamphetamine at 6-h intervals with or without nimodipine (1 mg/kg), and killed 1 or 18 h after the last drug administration. The decrease in hippocampal tryptophan hydroxylase activity induced by amphetamine and methamphetamine was potentiated by the administration of nimodipine. Moreover, while hippocampal tryptophan hydroxylase activity was not altered by 2.5 mg/kg methamphetamine alone, the coadministration of 1 mg/kg nimodipine decreased the enzymatic activity to 68% of control. The decrease in striatal tryptophan hydroxylase activity caused by these amphetamine analogues was not significantly altered by the coadministration of nimodipine. Interestingly, nimodipine increased hippocampal and striatal amphetamine concentrations to 187 and 162%, respectively, of the concentrations measured in animals treated with amphetamine alone. Nimodipine also increased by 2-fold the plasma concentration of methamphetamine and amphetamine measured 3 h after a single administration of methamphetamine, whereas the hippocampal concentrations of these compounds were raised to 354 and 516%, respectively, of that in animals treated with methamphetamine alone. These results suggest that nimodipine altered drug distribution and potentiated the methamphetamine-induced decrease in hippocampal tryptophan hydroxylase activity by increasing the cerebral methamphetamine concentration.     

杏仁核和扣带回联合毁损对MAP大鼠脑内多巴胺D2受体的影响

目的探讨联合毁损杏仁核和扣带回对甲基苯丙胺(M AP)大鼠脑内边缘区多巴胺D2受体表达的影响。方法40只SD大鼠随机分为对照组、M AP组、M AP 毁损组和M AP 假毁损组,每组各10只;采用经腹腔注射M AP制备精神分裂症M AP模型,立体定向-射频毁损杏仁核和扣带回,免疫组织化学ABC法观察边缘区D2受体的表达。结果与对照组和M AP 损毁组比较,M AP组及M AP 假毁损组大鼠边缘区D2受体表达有显著性差异(P<0.01);M AP 毁损组大鼠边缘区D2受体阳性细胞率与对照组比较差异无显著性(P>0.05)。结论杏仁核和扣带回的联合毁损可抑制使用M A P诱发的边缘区D2受体表达的亢进。     

Competitive and noncompetitive N-methyl-D-aspartate antagonists protect dopaminergic and serotonergic neurotoxicity produced by methamphetamine in various brain regions

Summary Protective effects of NMDA antagonists on dopaminergic and serotonergic neurotoxicity produced by methamphetamine (MA) were examined. Four injections of MA (7.5 mg/kg, s.c., at 2 h intervals) caused significant decrements (40–60% of control values) in levels of dopamine (DA) and its metabolites in the rat striatum and levels of serotonin (5-HT) and its metabolite in the medial prefrontal cortex, nucleus accumbens, striatum, anterior hypothalamus, amygdala and hippocampus. These decreases in DA, 5-HT and their metabolites were prevented by pretreatment with MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, or D-CPP-ene (SDZ EAA 494), a competitive NMDA antagonist. The results suggest that NMDA receptors play a role for MA-induced serotonergic damage in various brain regions as well as dopaminergic damage in the striatum.