Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic ...Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.展开更多
Effective detection of methamphetamine(Met)requires a fast,sensitive,and cheap testing assay.However,commercially available methods require expensive instruments and highly trained operators,which are time-consuming a...Effective detection of methamphetamine(Met)requires a fast,sensitive,and cheap testing assay.However,commercially available methods require expensive instruments and highly trained operators,which are time-consuming and labor-intensive.Herein,an antibody-modified graphene transistor assay is developed for sensitive and minute-level detection of Met in complex environments.The anti-Met probe captured charged targets within 120 s,leading to a p-doping effect near the graphene channel.The limit of detection reaches 50 aM(5.0×10^(-17)M)Met in solution.The graphene transistor would be a valuable tool for Met detection effective prevention of drug abuse.展开更多
The relapse of methamphetamine (meth) is associated with decision-making dysfunction. The present study aims to investigate theimpact of different emotions on the decision-making behavior of meth users. We used 2 (gen...The relapse of methamphetamine (meth) is associated with decision-making dysfunction. The present study aims to investigate theimpact of different emotions on the decision-making behavior of meth users. We used 2 (gender: male, female) × 3 (emotion:positive, negative, neutral) × 5 (block: 1, 2, 3, 4, 5) mixed experiment design. The study involved 168 meth users who weredivided into three groups: positive emotion, negative emotion and neutral emotion group, and tested by the emotional IowaGambling Task (IGT). The IGT performance of male users exhibited a decreasing trend from Block 1 to Block 3. Female methusers in positive emotion had the best performance in IGT than females in the other two groups. In positive emotion, the IGTperformance of female meth users was significantly better than that of men. Female meth users in positive emotion had betterdecision-making than those in negative or neutral emotion. Female meth users in positive emotion had better decision-makingperformance than males in positive emotion. In negative and neutral emotions, there was no significant gender difference indecision-making.展开更多
Background Methamphetamine (MA) is one of the most commonly abused illicit psychostimulant drugs and MA use disorder constitutes a universal health concern across the world. Despite many intervention approaches to MA ...Background Methamphetamine (MA) is one of the most commonly abused illicit psychostimulant drugs and MA use disorder constitutes a universal health concern across the world. Despite many intervention approaches to MA use disorder, the indicator of addiction severity is mainly limited to subjective craving score to drug-related cues, which is influenced by many factors such as social approval and self-masking. Aim The present study investigates whether self-reported craving for drug use in response to MA cues is a reliable indicator for addiction severity in MA users, and then tests the validity of the cue-induced attention bias test in addiction severity assessment. Methods Fifty-two male MA users completed the cueinduced craving test and attention bias task, and were required to report clinical characteristics of addiction severity. For the attention bias test, subjects were required to discriminate the letter superimposed onto MA userelated or neutral scenes. The reaction time delay during MA-use condition relative to neutral condition was used as an index of the attention bias. Results The results showed that 24 of the 52 MA users rated non-zero in cue-induced craving test, and they showed a significant attention bias to drug-related pictures. However, the other 28 users who rated zero in cue-induced craving evaluation showed a similar attention bias to drug-related cues. In addition, the attention bias to MA use-related cues was significantly and positively correlated with the clinical indexes of addiction severity, but the relationship was absent between subjective craving evaluation and the indexes of addiction severity. Conclusion These results suggest that attention bias to MA cues may be a more reliable indicator than experiential craving report, especially when subjective craving is measured in the compulsory rehabilitation centre.展开更多
Methamphetamine is one of the most prevalent drugs abused in the world.Methamphetamine abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric symptoms.However,the detailed mechanism under...Methamphetamine is one of the most prevalent drugs abused in the world.Methamphetamine abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric symptoms.However,the detailed mechanism underlying its neurotoxic action remains elusive.This study investigated the effects of methamphetamine + 39℃ on primary cortical neurons from the cortex of embryonic Sprague-Dawley rats.Primary cortex neurons were exposed to 1 mM methamphetamine + 39℃.Propidium iodide staining and lactate dehydrogenase release detection showed that methamphetamine + 39℃ triggered obvious necrosis-like death in cultured primary cortical neurons,which could be partially inhibited by receptor-interacting protein-1 (RIP1) inhibitor Necrostatin-1 partially.Western blot assay results showed that there were increases in the expressions of receptor-interacting protein-3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the primary cortical neurons treated with 1 mM methamphetamine + 39℃ for 3 hours.After pre-treatment with RIP3 inhibitor GSK’872,propidium iodide staining and lactate dehydrogenase release detection showed that neuronal necrosis rate was significantly decreased;RIP3 and MLKL protein expression significantly decreased.Immunohistochemistry staining results also showed that the expressions of RIP3 and MLKL were up-regulated in brain specimens from humans who had died of methamphetamine abuse.Taken together,the above results suggest that methamphetamine + 39℃ can induce RIP3/MLKL regulated necroptosis,thereby resulting in neurotoxicity.The study protocol was approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University,China (approval numbers: 2017-S026 and 2017-S033) on March 7,2017.展开更多
Methamphetamine is an amphetamine-type psychostimulant that can damage dopaminergic neurons and cause characteristic pathological changes similar to neurodegenerative diseases such as Parkinson's disease. However,...Methamphetamine is an amphetamine-type psychostimulant that can damage dopaminergic neurons and cause characteristic pathological changes similar to neurodegenerative diseases such as Parkinson's disease. However, its specific mechanism of action is still unclear. In the present study, we established a Parkinson's disease pathology model by exposing SH-SY5 Y cells and C57 BL/6 J mice to methamphetamine. In vitro experiments were performed with 0, 0.5, 1.0, 1.5, 2.0 or 2.5 mM methamphetamine for 24 hours or 2.0 mM methamphetamine for 0-, 2-, 4-, 8-, 16-, and 24-hour culture of SH-SY5 Y cells. Additional experimental groups of SH-SY5 Y cells were administered a nitric oxide inhibitor, 0.1 mM N-nitro-L-arginine, 1 hour before exposure to 2.0 mM methamphetamine for 24 hours. In vivo experiments: C57 BL/6 J mice were intraperitoneally injected with N-nitro-L-arginine(8 mg/kg), eight times, at intervals of 12 hours. Methamphetamine 15 mg/kg was intraperitoneally injected eight times, at intervals of 12 hours, but 0.5-hour after each N-nitro-L-arginine injection in the combined group. Western blot assay was used to determine the expression of nitric oxide synthase, α-synuclein(α-Syn), 5 G4, nitrated α-synuclein at the residue Tyr39(nT39 α-Syn), cleaved caspase-3, and cleaved poly ADP-ribose polymerase(PARP) in cells and mouse brain tissue. Immunofluorescence staining was conducted to measure the positive reaction of NeuN, nT39 α-Syn and 5 G4. Enzyme linked immunosorbent assay was performed to determine the dopamine levels in the mouse brain. After methamphetamine exposure, α-Syn expression increased; the aggregation of α-Syn 5 G4 increased; nT39 α-Syn, nitric oxide synthase, cleaved caspase-3, and cleaved PARP expression increased in the cultures of SH-SY5 Y cells and in the brains of C57 BL/6 J mice; and dopamine levels were reduced in the mouse brain. These changes were markedly reduced when N-nitro-L-arginine was administered with methamphetamine in both SH-SY5 Y cells and C57 BL/6 J mice. These results suggest that nT39 α-Syn aggregation is involved in methamphetamine neurotoxicity.展开更多
Aim p53 up-regulated modulator of apoptosis （PUMA） is a known apoptosis inducer; however its role in microglial survival remains poorly understood. In addition to the classical transcription factor p53, microRNA- ...Aim p53 up-regulated modulator of apoptosis （PUMA） is a known apoptosis inducer; however its role in microglial survival remains poorly understood. In addition to the classical transcription factor p53, microRNA- 143 （miR-143） is involved in PUMA expression at the post-transcriptional level. Furthermore, they identify unique roles of miR-143/PUMA in mediating microglial survival via the regulation of apoptosis and autophagy interplay. Results Blockage of autophagy accelerated methamphetamine-induced apoptosis, whereas the induction of autoph- agy attenuated the decrease in microglial survival. Moreover, anti-miR-143-dependent PUMA up-regulation re- versed the methamphetamine-induced decrease in microglial survival via the regulation of apoptosis and autophagy. The in vivo relevance of these findings was confirmed in mouse models, which demonstrated that the microinjection of anti-miR-143 into the hippocampus ameliorated the methamphetamine-induced decrease in microglia as well as that observed in heterozygous miR-143 ^＋/- mice. Conclusion These findings provided new insight for the specific contributions of miR-143/PUMA to microglial survival in the context of drug abuse.展开更多
BACKGROUND The rising number of people using methamphetamine leads to an increasing need for treatment options for this patient group.Evidence-based research on the efficacy of treatment programs for methamphetamine u...BACKGROUND The rising number of people using methamphetamine leads to an increasing need for treatment options for this patient group.Evidence-based research on the efficacy of treatment programs for methamphetamine users is limited.Due to specific characteristics of methamphetamine users,the question arises whether established treatment methods for individuals using other substances can be effective for the treatment of methamphetamine dependence as well.We hypothesize that there are significant differences between the two groups that may affect the effectiveness of treatment and worsen the prognosis of treatment outcomes for methamphetamine users compared to consumers of other substances.AIM To investigate potential differences in cognitive functioning and psychopathology between methamphetamine users and other substance users and possible correlations with treatment outcomes.METHODS A total of 110 subjects were recruited for an observational,longitudinal study from a German inpatient addiction treatment center:55 patients with methamphetamine dependence and 55 patients with dependence of other substances(“OS group”).Both groups were examined at beginning(baseline)and end of treatment(after 6 mo)with regard to treatment retention,craving,cognitive functioning,psychosocial resources,personality traits,depression,and other psychiatric symptoms.Instruments used were Raven’s IQ test,Mannheimer craving scale,cognitrone cognitive test battery,NEO personality factors inventory,Hamilton depression scale,Becks depression inventory,and a symptom checklist.The statistical methods used were χ^(2)-test,t-test and multiple mixed ANOVAs.RESULTS A total drop-out rate of 40%(methamphetamine-group:36.4%;OS-group:43.6%)was observed without significant differences between groups.At baseline,methamphetamine-group subjects significantly differed from OS-group individuals in terms of a lower intelligence quotient,fewer years of education,slower working speed,and decreased working accuracy,as well as less cannabinoid and cocaine use.Methamphetamine-group subjects further showed a significantly lower score of conscientiousness,depressive,and psychiatric symptoms than subjects from the OSgroup.In both groups,a reduction of craving and depressive symptoms and an improvement of working speed and working accuracy was noted after treatment.CONCLUSION There are differences between methamphetamine users and users of other drugs,but not with regard to the effectiveness of treatment in this inpatient setting.There are differences in cognitive function and psychopathology between methamphetamine and other drugs users.The existing treatment options seem to be an effective approach in treating methamphetamine dependence.展开更多
Use of new amphetamine-type stimulants (ATS) as designer drugs is a serious problem worldwide. ATS are used in tablet, capsule, and powder forms, and can be mixed with other drugs. There is little information availabl...Use of new amphetamine-type stimulants (ATS) as designer drugs is a serious problem worldwide. ATS are used in tablet, capsule, and powder forms, and can be mixed with other drugs. There is little information available on how these new drugs are metabolized or their ability to inhibit the metabolism of co-administered drugs. This study aimed to investigate the metabolism of six 4-substituted analogs of methamphetamine (MA), and their potential inhibition of MA metabolism. The metabolism of MA and the 4-substituted MAs was examined in vitro using human metabolic enzymes. Metabolite analyses were performed using trifluoroacetyl derivatization and GC-MS. The experiments showed that cytochrome P450 2D6 (CYP2D6) was involved in the major metabolic pathway of MA, where it catalyzed N-demethylation of 4-fluoromethamphetamine (4-FMA), 4-chloromethamphetamine (4-CMA), 4-bromomethamphetamine (4-BMA), 4-iodomethamphetamine (4-IMA) and 4-nitromethamphetamine (4-NMA), and O-demethylation of 4-methoxymethamphetamine (4-MMA). The half maximal inhibitory concentration (IC50) values for CYP2D6 using MA as substrate were different for each of the 4-substituted MAs. The strongest inhibitors of amphetamine production from MA were, in order, 4-IMA, 4-BMA, 4-CMA, 4-MMA, 4-FMA, and 4-NMA. The same order was observed for the IC50 values for inhibition of p-hydroxymethamphetamine production from MA, except for the IC50 of 4-MMA. The IC50 values of 4-IMA were lower than the IC50 values of fluoxetine and higher than that of quinidine. The results of this study imply that the risk of illicit drug interactions fluctuates so widely that unintentional fatal drug poisonings could occur.展开更多
Introduction: Relapse in methamphetamine dependency is one of the most difficult parts to treat. Therefore treatment of craving for usage is one of the essential sections of treatment in methamphetamine dependency (ad...Introduction: Relapse in methamphetamine dependency is one of the most difficult parts to treat. Therefore treatment of craving for usage is one of the essential sections of treatment in methamphetamine dependency (addiction). This study evaluates the effect of neurofeedback therapy on craving for use. Methods: In this study 20 male patient with methamphetamine dependency who diagnosed on the basis of DSM-V were selected. None of the patients had any psychiatric and neurologic disorder except addiction of methamphetamine. Patients were divided into 2 groups of 10. The first group has taken real neurofeedback therapy sessions while the second has undergone non-real neurofeedback (sham) therapy. Then the two groups have been compared with t-test. Result: The result shows that in the first group (real neurofeedback), craving for methamphetamine use has been decreased significantly whereas in the second group (non-real or sham), the decrease was not significant. Conclusion: Neurofeedback therapy is effective in treatment of craving for methamphetamine use.展开更多
Methamphetamine (METH), a highly addictive drug used worldwide, induces oxidative stress in various animal organs. Recent animal studies indicate that methamphetamine also induces oxidative stress in the retina, which...Methamphetamine (METH), a highly addictive drug used worldwide, induces oxidative stress in various animal organs. Recent animal studies indicate that methamphetamine also induces oxidative stress in the retina, which is an embryonic extension of the forebrain. The aim of this study, therefore, was to evaluate the protecttive effects of N-acetylcysteine amide (NACA) against oxidative stress induced by METH in retinal pigment epithelium (RPE) cells. Our studies showed that NACA protected against METH-induced oxidative stress in retinal pigment epithelial cells. Although METH significantly decreased glutathione (GSH) levels and increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, these returned to control levels with NACA treatment. Overall observations indicated that NACA protected RPE cells against oxidative cell damage and death by inhibiting lipid peroxidation, scavenging ROS, increasing levels of intracellular GSH, and maintaining the antioxidant enzyme activity and the integrity of the bloodretinal barrier (BRB). The effectiveness of NACA should be further evaluated to determine its potential for the treatment of numerous retinal diseases caused by oxidative stress.展开更多
With the proliferation of synthetic drugs,research on the mechanism of action of addictive drugs and treatment methods is of great significance.Among them,methamphetamine(METH)is the most representative amphetamine sy...With the proliferation of synthetic drugs,research on the mechanism of action of addictive drugs and treatment methods is of great significance.Among them,methamphetamine(METH)is the most representative amphetamine synthetic drug,and the treatment of METH addiction has become an urgent medical and social problem.In recent years,the therapeutic effects of Chinese herbal medicines on METH addiction have gained widespread attention because of their non-addictiveness,multiple targets,low side effects,low cost,and other characteristics.Previous studies have identified a variety of Chinese herbal medicines with effects on METH addiction.Based on the research on METH in recent years,this article summarizes the mechanism of action of METH as the starting point and briefly reviews the Chinese herbal medicine-based treatment of METH.展开更多
Methamphetamine(Meth)abuse can cause serious mental disorders,including anxiety and depression.The gut microbiota is a crucial contributor to maintaining host mental health.Here,we aim to investigate if microbiota par...Methamphetamine(Meth)abuse can cause serious mental disorders,including anxiety and depression.The gut microbiota is a crucial contributor to maintaining host mental health.Here,we aim to investigate if microbiota participate in Meth-induced mental disorders,and the potential mechanisms involved.Here,15 mg/kg Meth resulted in anxiety-and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor(SIGMAR1)/BDNF/TRKB pathway in the hippocampus.Mean-while,Meth impaired gut homeostasis by arousing the Toll-like receptor 4(TLR4)-related colonic inflammation,disturbing the gut microbiome and reducing the microbiota-derived short-chain fatty acids(SCFAs).Moreover,fecal microbiota from Meth-administrated mice mediated the colonic inflam-mation and reproduced anxiety-and depression-like behaviors in recipients.Further,SCFAs supple-mentation optimized Meth-induced microbial dysbiosis,ameliorated colonic inflammation,and repressed anxiety-and depression-like behaviors.Finally,Sigmarl knockout(Sigmar1^(-/-))repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure,and elim-inated the anti-anxiety and-depression effects of SCFAs.The activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety-and depression-like behaviors.Our findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis,and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent manner.This study confirms the crucial role of microbiota in Methrelated mental disorders and provides a potential preemptive therapy.展开更多
Background:Fingermark is an individual’s primary identification source.It is helpful in determining individuals involved in illegal activities and is frequently encountered in clandestine laboratories.During forensic...Background:Fingermark is an individual’s primary identification source.It is helpful in determining individuals involved in illegal activities and is frequently encountered in clandestine laboratories.During forensic investigation,the critical question to be answered is whether a fingermark was left on a surface before or after the initiation of an unlawful activity.Aims and Objectives:This study aimed to investigate the visualization of methamphetamine-contaminated fingermarks on glass surfaces and estimate the immediacy of their depositions.Materials and Methods:In this study,the prior-deposition contaminated fingermarks,i.e.,fingermarks deposited a surface priorly contaminated by methamphetamine,and the postdeposition contaminated fingermarks,i.e.,fingermarks deposited on a clean surface but subsequently contaminated with methamphetamine were visualized and compared using Field Emission Scanning Electron Microscope(FESEM).Results:Under FESEM,the latent fingermarks and the crystalline structure of methamphetamine were clearly visualized.The postdeposition contaminated fingermarks appeared in smudge conditions in all the three replicate samples,where the ridge and nonridge areas could not be well-distinguished.On the contrary,the prior-deposition contaminated fingermark demonstrated distinct separations between ridges and nonridges.However,the application of fingerprint powders reduced the possibility to determine the immediacy of deposition.Conclusion:To conclude,both prior-deposition contaminated fingermarks and postdeposition contaminated fingermarks can be discriminated,providing information on the instance when a fingermark was left on a surface.展开更多
Preclinical and clinical studies indicate that psychostimulants,in addition to having abuse potential,may elicit brain dysfunctions and/or neurotoxic effects.Central toxicity induced by psychostimulants may pose serio...Preclinical and clinical studies indicate that psychostimulants,in addition to having abuse potential,may elicit brain dysfunctions and/or neurotoxic effects.Central toxicity induced by psychostimulants may pose serious health risks since the recreational use of these substances is on the rise among young people and adults.The present review provides an overview of recent research,conducted between 2018 and 2023,focusing on brain dysfunctions and neurotoxic effects elicited in experimental models and humans by amphetamine,cocaine,methamphetamine,3,4-methylenedioxymethamphetamine,methylphenidate,caffeine,and nicotine.Detailed elucidation of factors and mechanisms that underlie psychostimulant-induced brain dysfunction and neurotoxicity is crucial for understanding the acute and enduring noxious brain effects that may occur in individuals who use psychostimulants for recreational and/or therapeutic purposes.展开更多
Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome.Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored str...Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome.Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA-target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine(MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR,LC-MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.展开更多
Methamphetamine(MA),an extremely addictive synthetic stimulant,has quickly spread to become the most frequently used illicit drug in China.People with a history of chronic and heavy MA use have a high possibility of e...Methamphetamine(MA),an extremely addictive synthetic stimulant,has quickly spread to become the most frequently used illicit drug in China.People with a history of chronic and heavy MA use have a high possibility of exhibiting schizophrenia-like psychotic symptoms,mainly delusions of reference,auditory hallucinations and cognitive deficits.These emerging findings suggest MA use increases aggression and violence and that there is a correlation between MA use and violence.However,it is unclear how to assess the capacity of criminal responsibility in“MA-induced”psychosis and how to set clear boundaries between schizophrenia and MA-induced psychosis when only limited and inconsistent evidence is available.Furthermore,a final persuasive differential diagnostic method based on improved understanding of schizophrenia and MA-induced psychotic disorders has yet to be developed.This paper will evaluate the epidemiology,social harm,and forensic psychiatric assessment of MA users,propose a future direction for the differential diagnosis between MA-induced psychotic disorders and schizophrenia,and put forward some practical solutions to assess the capacity of criminal responsibility of defendants with drug-induced psychotic disorder.展开更多
Postmortem investigation of methamphetamine(MA)abuse is an important task in forensic pathology.The present study investigated morphological changes in the astrocytes in the parietal cerebral cortex of MA abusers.Glia...Postmortem investigation of methamphetamine(MA)abuse is an important task in forensic pathology.The present study investigated morphological changes in the astrocytes in the parietal cerebral cortex of MA abusers.Glial fibrillary acidic protein immunoreactivity in the cerebral cortex was examined in forensic autopsy cases for MA-detected group and control group.Clasmatodendrotic astrocytes(including those with swollen cell bodies and disintegrating distal processes)were frequently observed in the cerebral cortex of MA abusers.Quantitative analysis using a colour image processor showed a concomitant increase in the astrocyte area and astrocyte-to-vessel area ratio(size and number of astrocytes)in the grey matter in acute MA fatality and other MA-involved cases,although the astrocyte area(size)was also increased in cases of asphyxiation.The total astrocyte area(size)in the white matter was significantly higher in MA fatalities and asphyxia than in the other groups involving MA abusers.Those indices were independent of blood MA level,age,sex,survival or postmortem time.These observations suggest the increasing number and hypertrophic changes of astrocytes in the grey matter in MA abusers can be the outcome of long-term abuse,while disintegrating distal processes may exist only in acute fatal MA intoxication.展开更多
In forensic medical examinations,estimating the postmortem interval(PMI)is an important factor.Methamphetamine(MA)is a synthetic stimulant that is commonly abused,and estimation of the PMI after MA abuse has become on...In forensic medical examinations,estimating the postmortem interval(PMI)is an important factor.Methamphetamine(MA)is a synthetic stimulant that is commonly abused,and estimation of the PMI after MA abuse has become one of the main tasks in forensic investigation.Microorganisms play a vital role in carrion decomposition.Analysing the bacterial succession patterns can be used as a forensic tool to estimate the PMI.The present study aimed to analyse bacterial succession changes during the decomposition of MA to estimate the PMI.We analysed bacterial communities in rabbits treated with three different concentrations of MA(0,22.5,and 90 mg/kg)under the natural conditions of 20°C and 70%humidity by sequencing 16S rRNA gene amplicons using the Illumina MiSeq system.We obtained 2374209 high-quality sequences and 2937 operational taxonomic units(OTUs).The relative abundances of the bacterial communities varied markedly in response to different MA concentrations.Interestingly,in response to the different concentrations of MA,Bacteroidetes became disparate in the rectum in the late PMI.Increased numbers of bacterial taxa were identified in the rectum and buccal cavity samples,except at the highest concentration of MA in the rectum samples when PMI was 0-h,than were present in live rabbits.Meanwhile,the PMI correlated significantly with bacterial succession at different taxonomic levels.Our results suggested that bacterial community succession could be used as a“microbial clock”to estimate the PMI in cases of MA-related death;however,further study is required to gain a deeper understanding of this concept.展开更多
The mechanism of myocardial injury induced by the cardiovascular toxicity of methamphetamine(MA)has been shown to depend onalterations in myocardial proteins caused by MA.Primary screening of the expression of myocard...The mechanism of myocardial injury induced by the cardiovascular toxicity of methamphetamine(MA)has been shown to depend onalterations in myocardial proteins caused by MA.Primary screening of the expression of myocardial proteins in a rat model of MA intoxicationwas achieved by combining two‑dimensional electrophoresis and mass spectrometry analyses,which revealed a total of 100 differentiallyexpressed proteins.Of these,13 displayed significantly altered expression.Moreover,Western blotting and real‑time reverse transcriptionquantitative polymerase chain reaction analyses of several relative proteins demonstrated that acute MA intoxication lowers protein expressionand mRNA transcription of aldehyde dehydrogenase‑2 and NADH dehydrogenase(ubiquinone)1 alpha subcomplex subunit 10.In contrast,MA intoxication elevated the protein expression and mRNA transcription of heat shock protein family B(small)member 1.By combiningbehavioral assessments of experimental rat models with the histological and pathological changes evident in cardiomyocytes,a mechanismaccounting for MA myocardial toxicity was suggested.MA alters the regulation of gene transcription and the subsequent expression of certainproteins that participate in myocardial respiration and in responding to oxidative stress,resulting in myocardial dysfunction and structuralchanges that affect the functioning of the cardiovascular system.展开更多
基金supported by the National Natural Science Foundation of China,No.81971246 (to TM)Opening Foundation of Jiangsu Key Laboratory of Neurodegeneration,Nanjing Medical University,No.KF202204 (to LZ and SF)。
文摘Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.
基金funded by the National Key R&D Program of China(No.2021YFE0201400)the National Natural Science Foundation of China(Nos.51773041,61890940,22066011)+3 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB30000000)the Department of Education of Jiangxi Province(No.GJJ211105)Jiangxi Science&Technology Normal University(No.2021QNBJRC002)State Key Laboratory of Molecular Engineering of Polymers.
文摘Effective detection of methamphetamine(Met)requires a fast,sensitive,and cheap testing assay.However,commercially available methods require expensive instruments and highly trained operators,which are time-consuming and labor-intensive.Herein,an antibody-modified graphene transistor assay is developed for sensitive and minute-level detection of Met in complex environments.The anti-Met probe captured charged targets within 120 s,leading to a p-doping effect near the graphene channel.The limit of detection reaches 50 aM(5.0×10^(-17)M)Met in solution.The graphene transistor would be a valuable tool for Met detection effective prevention of drug abuse.
基金supported by grants from the National Social Science Foundation of China(19BGL230)the Key Project of Social Science Planning in Jiangxi Province(23JY01).
文摘The relapse of methamphetamine (meth) is associated with decision-making dysfunction. The present study aims to investigate theimpact of different emotions on the decision-making behavior of meth users. We used 2 (gender: male, female) × 3 (emotion:positive, negative, neutral) × 5 (block: 1, 2, 3, 4, 5) mixed experiment design. The study involved 168 meth users who weredivided into three groups: positive emotion, negative emotion and neutral emotion group, and tested by the emotional IowaGambling Task (IGT). The IGT performance of male users exhibited a decreasing trend from Block 1 to Block 3. Female methusers in positive emotion had the best performance in IGT than females in the other two groups. In positive emotion, the IGTperformance of female meth users was significantly better than that of men. Female meth users in positive emotion had betterdecision-making than those in negative or neutral emotion. Female meth users in positive emotion had better decision-makingperformance than males in positive emotion. In negative and neutral emotions, there was no significant gender difference indecision-making.
基金National Natural Science Foundation of China (grant no. 3187110331671164).
文摘Background Methamphetamine (MA) is one of the most commonly abused illicit psychostimulant drugs and MA use disorder constitutes a universal health concern across the world. Despite many intervention approaches to MA use disorder, the indicator of addiction severity is mainly limited to subjective craving score to drug-related cues, which is influenced by many factors such as social approval and self-masking. Aim The present study investigates whether self-reported craving for drug use in response to MA cues is a reliable indicator for addiction severity in MA users, and then tests the validity of the cue-induced attention bias test in addiction severity assessment. Methods Fifty-two male MA users completed the cueinduced craving test and attention bias task, and were required to report clinical characteristics of addiction severity. For the attention bias test, subjects were required to discriminate the letter superimposed onto MA userelated or neutral scenes. The reaction time delay during MA-use condition relative to neutral condition was used as an index of the attention bias. Results The results showed that 24 of the 52 MA users rated non-zero in cue-induced craving test, and they showed a significant attention bias to drug-related pictures. However, the other 28 users who rated zero in cue-induced craving evaluation showed a similar attention bias to drug-related cues. In addition, the attention bias to MA use-related cues was significantly and positively correlated with the clinical indexes of addiction severity, but the relationship was absent between subjective craving evaluation and the indexes of addiction severity. Conclusion These results suggest that attention bias to MA cues may be a more reliable indicator than experiential craving report, especially when subjective craving is measured in the compulsory rehabilitation centre.
基金funded by the National Natural Science Foundation of China,No.81971891(to KX),81571939(to KX),81772134(to KX),81772024(to JY),and 81860781(to FXL)the Key Research and Development Program of Hunan Province of China,No.2018SK2091(to KX)+1 种基金the Natural Science Foundation of Hunan Province of China,No.2017JJ2339(to JY)the Wu Jie-Ping Medical Foundation of the Minister of Health of China,No.320.6750.14118(to KX)
文摘Methamphetamine is one of the most prevalent drugs abused in the world.Methamphetamine abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric symptoms.However,the detailed mechanism underlying its neurotoxic action remains elusive.This study investigated the effects of methamphetamine + 39℃ on primary cortical neurons from the cortex of embryonic Sprague-Dawley rats.Primary cortex neurons were exposed to 1 mM methamphetamine + 39℃.Propidium iodide staining and lactate dehydrogenase release detection showed that methamphetamine + 39℃ triggered obvious necrosis-like death in cultured primary cortical neurons,which could be partially inhibited by receptor-interacting protein-1 (RIP1) inhibitor Necrostatin-1 partially.Western blot assay results showed that there were increases in the expressions of receptor-interacting protein-3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the primary cortical neurons treated with 1 mM methamphetamine + 39℃ for 3 hours.After pre-treatment with RIP3 inhibitor GSK’872,propidium iodide staining and lactate dehydrogenase release detection showed that neuronal necrosis rate was significantly decreased;RIP3 and MLKL protein expression significantly decreased.Immunohistochemistry staining results also showed that the expressions of RIP3 and MLKL were up-regulated in brain specimens from humans who had died of methamphetamine abuse.Taken together,the above results suggest that methamphetamine + 39℃ can induce RIP3/MLKL regulated necroptosis,thereby resulting in neurotoxicity.The study protocol was approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University,China (approval numbers: 2017-S026 and 2017-S033) on March 7,2017.
基金supported by the National Natural Science Foundation of China,No.81373240(to PMQ)and 81671865(to PMQ)
文摘Methamphetamine is an amphetamine-type psychostimulant that can damage dopaminergic neurons and cause characteristic pathological changes similar to neurodegenerative diseases such as Parkinson's disease. However, its specific mechanism of action is still unclear. In the present study, we established a Parkinson's disease pathology model by exposing SH-SY5 Y cells and C57 BL/6 J mice to methamphetamine. In vitro experiments were performed with 0, 0.5, 1.0, 1.5, 2.0 or 2.5 mM methamphetamine for 24 hours or 2.0 mM methamphetamine for 0-, 2-, 4-, 8-, 16-, and 24-hour culture of SH-SY5 Y cells. Additional experimental groups of SH-SY5 Y cells were administered a nitric oxide inhibitor, 0.1 mM N-nitro-L-arginine, 1 hour before exposure to 2.0 mM methamphetamine for 24 hours. In vivo experiments: C57 BL/6 J mice were intraperitoneally injected with N-nitro-L-arginine(8 mg/kg), eight times, at intervals of 12 hours. Methamphetamine 15 mg/kg was intraperitoneally injected eight times, at intervals of 12 hours, but 0.5-hour after each N-nitro-L-arginine injection in the combined group. Western blot assay was used to determine the expression of nitric oxide synthase, α-synuclein(α-Syn), 5 G4, nitrated α-synuclein at the residue Tyr39(nT39 α-Syn), cleaved caspase-3, and cleaved poly ADP-ribose polymerase(PARP) in cells and mouse brain tissue. Immunofluorescence staining was conducted to measure the positive reaction of NeuN, nT39 α-Syn and 5 G4. Enzyme linked immunosorbent assay was performed to determine the dopamine levels in the mouse brain. After methamphetamine exposure, α-Syn expression increased; the aggregation of α-Syn 5 G4 increased; nT39 α-Syn, nitric oxide synthase, cleaved caspase-3, and cleaved PARP expression increased in the cultures of SH-SY5 Y cells and in the brains of C57 BL/6 J mice; and dopamine levels were reduced in the mouse brain. These changes were markedly reduced when N-nitro-L-arginine was administered with methamphetamine in both SH-SY5 Y cells and C57 BL/6 J mice. These results suggest that nT39 α-Syn aggregation is involved in methamphetamine neurotoxicity.
文摘Aim p53 up-regulated modulator of apoptosis （PUMA） is a known apoptosis inducer; however its role in microglial survival remains poorly understood. In addition to the classical transcription factor p53, microRNA- 143 （miR-143） is involved in PUMA expression at the post-transcriptional level. Furthermore, they identify unique roles of miR-143/PUMA in mediating microglial survival via the regulation of apoptosis and autophagy interplay. Results Blockage of autophagy accelerated methamphetamine-induced apoptosis, whereas the induction of autoph- agy attenuated the decrease in microglial survival. Moreover, anti-miR-143-dependent PUMA up-regulation re- versed the methamphetamine-induced decrease in microglial survival via the regulation of apoptosis and autophagy. The in vivo relevance of these findings was confirmed in mouse models, which demonstrated that the microinjection of anti-miR-143 into the hippocampus ameliorated the methamphetamine-induced decrease in microglia as well as that observed in heterozygous miR-143 ^＋/- mice. Conclusion These findings provided new insight for the specific contributions of miR-143/PUMA to microglial survival in the context of drug abuse.
基金the German Federal Ministry of Health(partially).
文摘BACKGROUND The rising number of people using methamphetamine leads to an increasing need for treatment options for this patient group.Evidence-based research on the efficacy of treatment programs for methamphetamine users is limited.Due to specific characteristics of methamphetamine users,the question arises whether established treatment methods for individuals using other substances can be effective for the treatment of methamphetamine dependence as well.We hypothesize that there are significant differences between the two groups that may affect the effectiveness of treatment and worsen the prognosis of treatment outcomes for methamphetamine users compared to consumers of other substances.AIM To investigate potential differences in cognitive functioning and psychopathology between methamphetamine users and other substance users and possible correlations with treatment outcomes.METHODS A total of 110 subjects were recruited for an observational,longitudinal study from a German inpatient addiction treatment center:55 patients with methamphetamine dependence and 55 patients with dependence of other substances(“OS group”).Both groups were examined at beginning(baseline)and end of treatment(after 6 mo)with regard to treatment retention,craving,cognitive functioning,psychosocial resources,personality traits,depression,and other psychiatric symptoms.Instruments used were Raven’s IQ test,Mannheimer craving scale,cognitrone cognitive test battery,NEO personality factors inventory,Hamilton depression scale,Becks depression inventory,and a symptom checklist.The statistical methods used were χ^(2)-test,t-test and multiple mixed ANOVAs.RESULTS A total drop-out rate of 40%(methamphetamine-group:36.4%;OS-group:43.6%)was observed without significant differences between groups.At baseline,methamphetamine-group subjects significantly differed from OS-group individuals in terms of a lower intelligence quotient,fewer years of education,slower working speed,and decreased working accuracy,as well as less cannabinoid and cocaine use.Methamphetamine-group subjects further showed a significantly lower score of conscientiousness,depressive,and psychiatric symptoms than subjects from the OSgroup.In both groups,a reduction of craving and depressive symptoms and an improvement of working speed and working accuracy was noted after treatment.CONCLUSION There are differences between methamphetamine users and users of other drugs,but not with regard to the effectiveness of treatment in this inpatient setting.There are differences in cognitive function and psychopathology between methamphetamine and other drugs users.The existing treatment options seem to be an effective approach in treating methamphetamine dependence.
文摘Use of new amphetamine-type stimulants (ATS) as designer drugs is a serious problem worldwide. ATS are used in tablet, capsule, and powder forms, and can be mixed with other drugs. There is little information available on how these new drugs are metabolized or their ability to inhibit the metabolism of co-administered drugs. This study aimed to investigate the metabolism of six 4-substituted analogs of methamphetamine (MA), and their potential inhibition of MA metabolism. The metabolism of MA and the 4-substituted MAs was examined in vitro using human metabolic enzymes. Metabolite analyses were performed using trifluoroacetyl derivatization and GC-MS. The experiments showed that cytochrome P450 2D6 (CYP2D6) was involved in the major metabolic pathway of MA, where it catalyzed N-demethylation of 4-fluoromethamphetamine (4-FMA), 4-chloromethamphetamine (4-CMA), 4-bromomethamphetamine (4-BMA), 4-iodomethamphetamine (4-IMA) and 4-nitromethamphetamine (4-NMA), and O-demethylation of 4-methoxymethamphetamine (4-MMA). The half maximal inhibitory concentration (IC50) values for CYP2D6 using MA as substrate were different for each of the 4-substituted MAs. The strongest inhibitors of amphetamine production from MA were, in order, 4-IMA, 4-BMA, 4-CMA, 4-MMA, 4-FMA, and 4-NMA. The same order was observed for the IC50 values for inhibition of p-hydroxymethamphetamine production from MA, except for the IC50 of 4-MMA. The IC50 values of 4-IMA were lower than the IC50 values of fluoxetine and higher than that of quinidine. The results of this study imply that the risk of illicit drug interactions fluctuates so widely that unintentional fatal drug poisonings could occur.
文摘Introduction: Relapse in methamphetamine dependency is one of the most difficult parts to treat. Therefore treatment of craving for usage is one of the essential sections of treatment in methamphetamine dependency (addiction). This study evaluates the effect of neurofeedback therapy on craving for use. Methods: In this study 20 male patient with methamphetamine dependency who diagnosed on the basis of DSM-V were selected. None of the patients had any psychiatric and neurologic disorder except addiction of methamphetamine. Patients were divided into 2 groups of 10. The first group has taken real neurofeedback therapy sessions while the second has undergone non-real neurofeedback (sham) therapy. Then the two groups have been compared with t-test. Result: The result shows that in the first group (real neurofeedback), craving for methamphetamine use has been decreased significantly whereas in the second group (non-real or sham), the decrease was not significant. Conclusion: Neurofeedback therapy is effective in treatment of craving for methamphetamine use.
文摘Methamphetamine (METH), a highly addictive drug used worldwide, induces oxidative stress in various animal organs. Recent animal studies indicate that methamphetamine also induces oxidative stress in the retina, which is an embryonic extension of the forebrain. The aim of this study, therefore, was to evaluate the protecttive effects of N-acetylcysteine amide (NACA) against oxidative stress induced by METH in retinal pigment epithelium (RPE) cells. Our studies showed that NACA protected against METH-induced oxidative stress in retinal pigment epithelial cells. Although METH significantly decreased glutathione (GSH) levels and increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, these returned to control levels with NACA treatment. Overall observations indicated that NACA protected RPE cells against oxidative cell damage and death by inhibiting lipid peroxidation, scavenging ROS, increasing levels of intracellular GSH, and maintaining the antioxidant enzyme activity and the integrity of the bloodretinal barrier (BRB). The effectiveness of NACA should be further evaluated to determine its potential for the treatment of numerous retinal diseases caused by oxidative stress.
基金Supported by Sichuan Provincial Science and Technology Department(No.2022YFS0635)Luzhou Science and Technology Bureau(No.2021LZXNYD-Z09)。
文摘With the proliferation of synthetic drugs,research on the mechanism of action of addictive drugs and treatment methods is of great significance.Among them,methamphetamine(METH)is the most representative amphetamine synthetic drug,and the treatment of METH addiction has become an urgent medical and social problem.In recent years,the therapeutic effects of Chinese herbal medicines on METH addiction have gained widespread attention because of their non-addictiveness,multiple targets,low side effects,low cost,and other characteristics.Previous studies have identified a variety of Chinese herbal medicines with effects on METH addiction.Based on the research on METH in recent years,this article summarizes the mechanism of action of METH as the starting point and briefly reviews the Chinese herbal medicine-based treatment of METH.
基金supported by the National Natural Science Foundation of China under Grant No.82171877the Department of Science and Technology of Guangzhou city under Grant No.202002030043(China)the Guangdong Natural Science Foundation under Grant No.2021A1515012456(China).
文摘Methamphetamine(Meth)abuse can cause serious mental disorders,including anxiety and depression.The gut microbiota is a crucial contributor to maintaining host mental health.Here,we aim to investigate if microbiota participate in Meth-induced mental disorders,and the potential mechanisms involved.Here,15 mg/kg Meth resulted in anxiety-and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor(SIGMAR1)/BDNF/TRKB pathway in the hippocampus.Mean-while,Meth impaired gut homeostasis by arousing the Toll-like receptor 4(TLR4)-related colonic inflammation,disturbing the gut microbiome and reducing the microbiota-derived short-chain fatty acids(SCFAs).Moreover,fecal microbiota from Meth-administrated mice mediated the colonic inflam-mation and reproduced anxiety-and depression-like behaviors in recipients.Further,SCFAs supple-mentation optimized Meth-induced microbial dysbiosis,ameliorated colonic inflammation,and repressed anxiety-and depression-like behaviors.Finally,Sigmarl knockout(Sigmar1^(-/-))repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure,and elim-inated the anti-anxiety and-depression effects of SCFAs.The activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety-and depression-like behaviors.Our findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis,and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent manner.This study confirms the crucial role of microbiota in Methrelated mental disorders and provides a potential preemptive therapy.
基金Universiti Sains Malaysia RUI grant(1001/PPSK/8012236).
文摘Background:Fingermark is an individual’s primary identification source.It is helpful in determining individuals involved in illegal activities and is frequently encountered in clandestine laboratories.During forensic investigation,the critical question to be answered is whether a fingermark was left on a surface before or after the initiation of an unlawful activity.Aims and Objectives:This study aimed to investigate the visualization of methamphetamine-contaminated fingermarks on glass surfaces and estimate the immediacy of their depositions.Materials and Methods:In this study,the prior-deposition contaminated fingermarks,i.e.,fingermarks deposited a surface priorly contaminated by methamphetamine,and the postdeposition contaminated fingermarks,i.e.,fingermarks deposited on a clean surface but subsequently contaminated with methamphetamine were visualized and compared using Field Emission Scanning Electron Microscope(FESEM).Results:Under FESEM,the latent fingermarks and the crystalline structure of methamphetamine were clearly visualized.The postdeposition contaminated fingermarks appeared in smudge conditions in all the three replicate samples,where the ridge and nonridge areas could not be well-distinguished.On the contrary,the prior-deposition contaminated fingermark demonstrated distinct separations between ridges and nonridges.However,the application of fingerprint powders reduced the possibility to determine the immediacy of deposition.Conclusion:To conclude,both prior-deposition contaminated fingermarks and postdeposition contaminated fingermarks can be discriminated,providing information on the instance when a fingermark was left on a surface.
基金supported by PON AIM(PON RICERCA E INNOVAZIONE 2014-2020,-AZIONE I.2.D.D.N.407 DEL 27 FEBBRAIO 2018-“ATTRACTION AND INTERNATIONAL MOBILITY”)(to GC)Zardi-Gori Foundation(research grant 2021)(to MS)+1 种基金intramural funds from the University of Cagliari(to NS)Fondazione CON IL SUD and The U.S.-Italy Fulbright Commission(to AEP).
文摘Preclinical and clinical studies indicate that psychostimulants,in addition to having abuse potential,may elicit brain dysfunctions and/or neurotoxic effects.Central toxicity induced by psychostimulants may pose serious health risks since the recreational use of these substances is on the rise among young people and adults.The present review provides an overview of recent research,conducted between 2018 and 2023,focusing on brain dysfunctions and neurotoxic effects elicited in experimental models and humans by amphetamine,cocaine,methamphetamine,3,4-methylenedioxymethamphetamine,methylphenidate,caffeine,and nicotine.Detailed elucidation of factors and mechanisms that underlie psychostimulant-induced brain dysfunction and neurotoxicity is crucial for understanding the acute and enduring noxious brain effects that may occur in individuals who use psychostimulants for recreational and/or therapeutic purposes.
基金funded by Korea Institute of Science and Technology Intramural Funding (2E26640,2E30952Republic of Korea)+7 种基金National Research Council of Science & Technology (NST) grant by Korean government (MSIP) (CRC-15-04-KISTRepublic of Korea)Center for Women In Science,Engineering,and Technology (WISET) grant by Korean government (WISET2020-525Republic of Korea)National Research Foundation of Korea (2017R1A2B2003993,2020R1A2C2004610Republic of Korea)UST Young Scientist Research Program through Korea University of Science and Technology (UST) (2017YS03Republic of Korea)。
文摘Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome.Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA-target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine(MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR,LC-MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.
基金supported by grants from the National Natu-ral Science Foundation of China[grant number 81530061].
文摘Methamphetamine(MA),an extremely addictive synthetic stimulant,has quickly spread to become the most frequently used illicit drug in China.People with a history of chronic and heavy MA use have a high possibility of exhibiting schizophrenia-like psychotic symptoms,mainly delusions of reference,auditory hallucinations and cognitive deficits.These emerging findings suggest MA use increases aggression and violence and that there is a correlation between MA use and violence.However,it is unclear how to assess the capacity of criminal responsibility in“MA-induced”psychosis and how to set clear boundaries between schizophrenia and MA-induced psychosis when only limited and inconsistent evidence is available.Furthermore,a final persuasive differential diagnostic method based on improved understanding of schizophrenia and MA-induced psychotic disorders has yet to be developed.This paper will evaluate the epidemiology,social harm,and forensic psychiatric assessment of MA users,propose a future direction for the differential diagnosis between MA-induced psychotic disorders and schizophrenia,and put forward some practical solutions to assess the capacity of criminal responsibility of defendants with drug-induced psychotic disorder.
基金funded by Natural Science Foundation of Guangdong Province[Grant Number 2015A030313110]Shanghai Key Lab of Forensic Medicine[Grant Number KF1503].
文摘Postmortem investigation of methamphetamine(MA)abuse is an important task in forensic pathology.The present study investigated morphological changes in the astrocytes in the parietal cerebral cortex of MA abusers.Glial fibrillary acidic protein immunoreactivity in the cerebral cortex was examined in forensic autopsy cases for MA-detected group and control group.Clasmatodendrotic astrocytes(including those with swollen cell bodies and disintegrating distal processes)were frequently observed in the cerebral cortex of MA abusers.Quantitative analysis using a colour image processor showed a concomitant increase in the astrocyte area and astrocyte-to-vessel area ratio(size and number of astrocytes)in the grey matter in acute MA fatality and other MA-involved cases,although the astrocyte area(size)was also increased in cases of asphyxiation.The total astrocyte area(size)in the white matter was significantly higher in MA fatalities and asphyxia than in the other groups involving MA abusers.Those indices were independent of blood MA level,age,sex,survival or postmortem time.These observations suggest the increasing number and hypertrophic changes of astrocytes in the grey matter in MA abusers can be the outcome of long-term abuse,while disintegrating distal processes may exist only in acute fatal MA intoxication.
基金This study was supported by the National Natural Science Foundation of China[Grant No.81772026,820721140].
文摘In forensic medical examinations,estimating the postmortem interval(PMI)is an important factor.Methamphetamine(MA)is a synthetic stimulant that is commonly abused,and estimation of the PMI after MA abuse has become one of the main tasks in forensic investigation.Microorganisms play a vital role in carrion decomposition.Analysing the bacterial succession patterns can be used as a forensic tool to estimate the PMI.The present study aimed to analyse bacterial succession changes during the decomposition of MA to estimate the PMI.We analysed bacterial communities in rabbits treated with three different concentrations of MA(0,22.5,and 90 mg/kg)under the natural conditions of 20°C and 70%humidity by sequencing 16S rRNA gene amplicons using the Illumina MiSeq system.We obtained 2374209 high-quality sequences and 2937 operational taxonomic units(OTUs).The relative abundances of the bacterial communities varied markedly in response to different MA concentrations.Interestingly,in response to the different concentrations of MA,Bacteroidetes became disparate in the rectum in the late PMI.Increased numbers of bacterial taxa were identified in the rectum and buccal cavity samples,except at the highest concentration of MA in the rectum samples when PMI was 0-h,than were present in live rabbits.Meanwhile,the PMI correlated significantly with bacterial succession at different taxonomic levels.Our results suggested that bacterial community succession could be used as a“microbial clock”to estimate the PMI in cases of MA-related death;however,further study is required to gain a deeper understanding of this concept.
基金Supported by Beijing Natural Science Foundation(7132116).
文摘The mechanism of myocardial injury induced by the cardiovascular toxicity of methamphetamine(MA)has been shown to depend onalterations in myocardial proteins caused by MA.Primary screening of the expression of myocardial proteins in a rat model of MA intoxicationwas achieved by combining two‑dimensional electrophoresis and mass spectrometry analyses,which revealed a total of 100 differentiallyexpressed proteins.Of these,13 displayed significantly altered expression.Moreover,Western blotting and real‑time reverse transcriptionquantitative polymerase chain reaction analyses of several relative proteins demonstrated that acute MA intoxication lowers protein expressionand mRNA transcription of aldehyde dehydrogenase‑2 and NADH dehydrogenase(ubiquinone)1 alpha subcomplex subunit 10.In contrast,MA intoxication elevated the protein expression and mRNA transcription of heat shock protein family B(small)member 1.By combiningbehavioral assessments of experimental rat models with the histological and pathological changes evident in cardiomyocytes,a mechanismaccounting for MA myocardial toxicity was suggested.MA alters the regulation of gene transcription and the subsequent expression of certainproteins that participate in myocardial respiration and in responding to oxidative stress,resulting in myocardial dysfunction and structuralchanges that affect the functioning of the cardiovascular system.
