Baclofen facilitates the extinction of methamphetamine-induced conditioned place preference in rats.

The powerful, long-lasting association between the rewarding effects of a drug and contextual cues associated with drug administration can be studied using conditioned place preference (CPP). The GABAB receptor agonist baclofen facilitates the extinction of morphine-induced CPP in mice. The current study extended this work by determining if baclofen could enhance the extinction of methamphetamine (Meth) CPP. CPP was established using a six-day conditioning protocol wherein Meth-pairings were alternated with saline-pairings. Rats were subsequently administered baclofen (2 mg/kg i.p. or vehicle) immediately after each daily forced extinction session, which consisted of a saline injection immediately prior to being placed into the previously Meth- or saline-paired chamber. One extinction training cycle, consisted of six once-daily forced extinction sessions, mimicking the alternating procedure established during conditioning, followed by a test for preference (Ext test). CPP persisted for at least four extinction cycles in vehicle-treated rats. In contrast, CPP was inhibited following a single extinction training cycle. These data indicate that Meth-induced CPP was resistant to extinction, but extinction training was rendered effective when the training was combined with baclofen. These findings converge with the prior demonstration of baclofen facilitating the extinction of morphine-induced CPP indicating that GABAB receptor actions are independent of the primary (unconditioned) stimulus (i.e., the opiate or the stimulant) and likely reflect mechanisms engaged by extinction learning processes per se. Thus, baclofen administered in conjunction with extinction training may be of value for addiction therapy regardless of the class of drug being abused. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Novel carboxymethyl derivatives of chitin and chitosan materials and their biomedical applications

Chitin and chitosan are natural biopolymers that are non-toxic, biodegradable and biocompatible. In the last decade, chitin and chitosan derivatives have garnered significant interest in the biomedical and biopharmaceutical research fields with applications as biomaterials for tissue engineering and wound healing and as excipients for drug delivery. Introducing small chemical groups to the chitin or chitosan structure, such as alkyl or carboxymethyl groups, can drastically increase the solubility of chitin and chitosan at neutral and alkaline pH values without affecting their characteristics; substitution with carboxyl groups can yield polymers with polyampholytic properties. Carboxymethyl derivatives of chitin and chitosan have shown promise for adsorbing metal ions, as drug delivery systems, in wound healing, as anti-microbial agents, in tissue engineering, as components in cosmetics and food and for anti-tumor activities. This review will focus on the preparative methods and applications of carboxymethyl and succinyl derivatives of chitin and chitosan with particular emphasis on their uses as materials for biomedical applications.     

The effects of modafinil treatment on neuropsychological and attentional bias performance during 7-day inpatient withdrawal from methamphetamine dependence.

The cognitive benefits of modafinil to patients undergoing 7-day inpatient withdrawal from methamphetamine (MA) dependence were examined as part of a double-blind, randomized, placebo-controlled pilot trial. Recent evidence has identified modafinil-related improvements in treatment outcomes for MA-dependent patients; however, the benefits to cognition function, which is critical to treatment success but known to be impaired, has yet to be examined. The first 20 participants recruited to the study were administered either 200 mg of modafinil (once daily) or placebo, and a neuropsychological test battery (including an MA version of the emotional Stroop task) at admission (n = 17) and discharge (n = 14). Follow-up interviews were conducted at 1-month postdischarge (n = 13). After participant withdrawals (3 in each group), treatment was associated with a significant improvement in immediate verbal memory recall and nonsignificant trend toward improvement on executive function and delayed memory tasks. No benefit was seen for measures of verbal learning, visual memory, processing speed, or verbal fluency. All participants showed a significant attentional bias for MA-related stimuli on the emotional Stroop task. The magnitude of bias predicted both retention in treatment and relapse potential at follow-up but was not significantly ameliorated by modafinil treatment. While nonsignificant, the effect sizes of modafinil-related improvements in executive function and memory were consistent with those found in more robustly powered studies of cognitive benefits in attention-deficit/hyperactivity disorder and schizophrenia, supporting the need for further research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparative Neuropharmacology and Pharmacokinetics of Methamphetamine and Its Thiophene Analog Methiopropamine in Rodents

Methiopropamine is a novel psychoactive substance (NPS) that is associated with several cases of clinical toxicity, yet little information is available regarding its neuropharmacological properties. Here, we employed in vitro and in vivo methods to compare the pharmacokinetics and neurobiological effects of methiopropamine and its structural analog methamphetamine. Methiopropamine was rapidly distributed to the blood and brain after injection in C57BL/6 mice, with a pharmacokinetic profile similar to that of methamphetamine. Methiopropamine induced psychomotor activity, but higher doses were needed (E_max 12.5 mg/kg; i.p.) compared to methamphetamine (E_max 3.75 mg/kg; i.p.). A steep increase in locomotor activity was seen after a modest increase in the methiopropamine dose from 10 to 12.5 mg/kg, suggesting that a small increase in dosage may engender unexpectedly strong effects and heighten the risk of unintended overdose in NPS users. In vitro studies revealed that methiopropamine mediates its effects through inhibition of norepinephrine and dopamine uptake into presynaptic nerve terminals (IC₅₀ = 0.47 and 0.74 µM, respectively), while the plasmalemmal serotonin uptake and vesicular uptake are affected only at high concentrations (IC₅₀ > 25 µM). In summary, methiopropamine closely resembles methamphetamine with regard to its pharmacokinetics, pharmacodynamic effects and mechanism of action, with a potency that is approximately five times lower than that of methamphetamine.     

Biochemical Neuroadaptations in the Rat Striatal Dopaminergic System after Prolonged Exposure to Methamphetamine Self-Administration

Perturbations in striatal dopamine (DA) homeostasis might underlie the behavioral and pathobiological consequences of METH use disorder in humans. To identify potential consequences of long-term METH exposure, we modeled the adverse consequence DSM criterion of substance use disorders by giving footshocks to rats that had escalated their intake of METH during a drug self-administration procedure. Next, DA D1 receptor antagonist, SCH23390 was injected. Thereafter, rats were euthanized to measure several indices of the striatal dopaminergic system. Footshocks split the METH rats into two phenotypes: (i) shock-sensitive that decreased their METH-intake and (ii) shock-resistant that continued their METH intake. SCH23390 caused substantial dose-dependent reduction of METH taking in both groups. Stopping SCH23390 caused re-emergence of compulsive METH taking in shock-resistant rats. Compulsive METH takers also exhibited greater incubation of METH seeking than non-compulsive rats during withdrawal from METH SA. Analyses of DA metabolism revealed non-significant decreases (about 35%) in DA levels in resistant and sensitive rats. However, striatal contents of the deaminated metabolites, DOPAL and DOPAC, were significantly increased in sensitive rats. VMAT2 and DAT protein levels were decreased in both phenotypes. Moreover, protein expression levels of the D1-like DA receptor, D5R, and D2-like DA receptors, D3R and D4R, were significantly decreased in the compulsive METH takers. Our results parallel findings in post-mortem striatal tissues of human METH users who develop Parkinsonism after long-term METH intake and support the use of this model to investigate potential therapeutic interventions for METH use disorder.     

表面解吸常压化学电离质谱法快速测定冰毒

A method for rapid determination of narcotics by surface desorption atmospheric pressure chemical ionization mass spectrometry (DAPCI-MS) was established. The operation parameters including spray voltage, capillary temperature ect. on analysis performance were systematically investigated. Under the optimized experimental conditions, trace amounts of methamphetamine and caffeine in ice drug were detected rapidly without any sample preparation and pretreatment. Since DAPCI-MS allows rapid analyzing trace amounts of narcotics without sample pretreatment, it was also proposed to couple DAPCI source to a miniature mass spectrometer for fast in-situ analysis of narcotics．     

Family conflict and depression in HIV-negative heterosexuals: The role of methamphetamine use.

Previous research has reported elevated levels of depressive symptoms among methamphetamine users, but little attention has been paid to possible links between family environment and psychological distress. This study examined relationships between family conflict, substance use, and depressive symptoms in a sample of 104 heterosexual methamphetamine users in San Diego, California. Eighty-nine percent of the sample reported conflict with a family member in the past year. Conflict was reported most often with parents and siblings. Sources of conflict included drug use, lifestyle issues, interpersonal and communication issues, and concern for other family members. In regression analyses, being female, being a polydrug user, and facing social and legal stressors were associated with higher levels of family conflict. Multiple regression analyses also revealed a positive association between family conflict and depressive symptoms. Contrary to expectation, methamphetamine dose did not moderate the relationship between family conflict and depressive symptoms. Reducing family conflict may be an important first step toward ameliorating depressive symptoms and creating more supportive environments for methamphetamine users who are in urgent need of effective interventions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Depression ratings, reported sexual risk behaviors, and methamphetamine use: Latent growth curve models of positive change among gay and bisexual men in an outpatient treatment program.

Although the cessation of substance use is the principal concern of drug treatment programs, many individuals in treatment experience co-occurring problems such as mood disruptions and sexual risk behaviors that may complicate their recovery process. This study assessed relationships among dynamic changes tracked over time in methamphetamine use, depression symptoms, and sexual risk behaviors (unprotected anal intercourse) in a sample of 145 methamphetamine-dependent gay and bisexual males enrolled in a 16-week outpatient drug treatment research program. Participants were randomly assigned into 1 of 4 conditions: contingency management (CM), cognitive behavioral therapy (CBT; the control condition), combined CM and CBT, and a tailored gay-specific version of the CBT condition. Using latent growth curve models, the authors assessed the relationship of means (intercepts) and the slopes of the 3 measures of interest over time to test whether changes in methamphetamine use predicted declining rates of depression and risky sexual behavior in tandem. Participants with the greatest downward trajectory in methamphetamine use (urine verified) reported the greatest and quickest decreases in reported depressive symptoms and sexual risk behaviors. The control group reported the most methamphetamine use over the 16 weeks; the tailored gay-specific group reported a more rapidly decreasing slope in methamphetamine use than the other participants. Findings indicate that lowering methamphetamine use itself has a concurrent and synergistic effect on depressive symptoms and risky sexual behavior patterns. This suggests that some users who respond well to treatment may show improvement in these co-occurring problems without a need for more intensive targeted interventions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

毛发中违禁苯丙胺类的代谢研究

应用 GC/MS技术 ,鉴定、确认了毛发中 MAMP、MDMA和芬氟拉明的代谢物 AMP、MDA和去乙基芬氟拉明的存在 ;建立了 GC/MS/SIM法测定毛发中苯丙胺类及代谢产物的定性定量分析方法 ,毛发用量少 ( 1 0 mg)、灵敏度高( 0 .1 ng.mg)、特异性强。方法应用于考察 MAMP、MDMA和芬氟拉明在豚鼠毛发中的时间过程和浓度变化状况 ,并成功地用于涉毒案件的鉴定。     

Comparison of the effects of methamphetamine, bupropion, and methylphenidate on the self-administration of methamphetamine by rhesus monkeys.

The effectiveness of methadone as a treatment for opioid abuse and nicotine preparations as treatments for tobacco smoking has led to an interest in developing a similar strategy for treating psychostimulant abuse. The current study investigated the effects of three such potential therapies on intravenous methamphetamine self-administration (1 – 30 μg/kg/injection) in rhesus monkeys. When given as a presession intramuscular injection, a high dose of methamphetamine (1.0 mg/kg) decreased intravenous methamphetamine self-administration but did not affect responding for a food reinforcer during the same sessions. However, the dose of intramuscular methamphetamine required to reduce intravenous methamphetamine self-administration exceeded the cumulative amount taken during a typical self-administration session, and pretreatment with a low dose of methamphetamine (0.3 mg/kg) actually increased self-administration in some monkeys at the lower self-administration dose. Like pretreatment with methamphetamine, pretreatment with bupropion (3.2 mg/kg) decreased methamphetamine self-administration but did not affect responding for food. Pretreatment with methylphenidate (0.56 mg/kg) did not significantly alter methamphetamine self-administration. These results suggest that some agonist-like agents can decrease methamphetamine self-administration. Although the most robust effects occurred with a high dose of methamphetamine, safety and abuse liability considerations suggest that bupropion should also be considered for further evaluation as a methamphetamine addiction treatment. (PsycINFO Database Record (c) 2011 APA, all rights reserved)