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1.
Sci Adv ; 9(2): eadd8417, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36630507

RESUMO

Amphetamine (AMPH) is a psychostimulant that is commonly abused. The stimulant properties of AMPH are associated with its ability to increase dopamine (DA) neurotransmission. This increase is promoted by nonvesicular DA release mediated by reversal of DA transporter (DAT) function. Syntaxin 1 (Stx1) is a SNARE protein that is phosphorylated at Ser14 by casein kinase II. We show that Stx1 phosphorylation is critical for AMPH-induced nonvesicular DA release and, in Drosophila melanogaster, regulates the expression of AMPH-induced preference and sexual motivation. Our molecular dynamics simulations of the DAT/Stx1 complex demonstrate that phosphorylation of these proteins is pivotal for DAT to dwell in a DA releasing state. This state is characterized by the breakdown of two key salt bridges within the DAT intracellular gate, causing the opening and hydration of the DAT intracellular vestibule, allowing DA to bind from the cytosol, a mechanism that we hypothesize underlies nonvesicular DA release.


Assuntos
Dopamina , Drosophila melanogaster , Animais , Dopamina/metabolismo , Sintaxina 1/metabolismo , Fosforilação , Drosophila melanogaster/metabolismo , Anfetamina/farmacologia
2.
BMC Psychiatry ; 23(1): 23, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627601

RESUMO

BACKGROUND: Illicit amphetamine-type stimulants (ATS) trafficking activities have increased substantially in Saudi Arabia over the last 10 years. In the period 2013-2017 Saudi Arabia seized the largest quantities of amphetamine at the global level. The current study examines whether the increased quantity of ATS seizures has an impact on amphetamine use disorder admissions. METHOD: This is an ecological study combining two datasets, the first dataset was obtained from United Nations Office on Drugs and Crime (UNODC), and the Al-Amal Hospital Electronic Health Record System in the city of Dammam, Eastern region of Saudi Arabia from 2005 to 2018. The annual incidence of patients diagnosed with amphetamine use was the dependent variable. The independent variable was the annual reported count of seized quantities of ATS in Saudi Arabia. We used a random intercept Negative Binomial model to predict the yearly count of amphetamine use disorder admission rates. RESULTS: A total of 910 amphetamine disorder admission patients in Al-Amal rehabilitation and addiction center, and the quantity equivalent to 200 tons of ATS was seized from 2005 to 2018. The amphetamine disorder admission rate has increased from 1.33% in 2005 to 18.27% in 2018. For each one-unit increase in the amphetamine confiscated quantities, the amphetamine use disorder admission rate increased by 49 to 88%. CONCLUSION: The current study found that reported amphetamine seized quantities were significantly and positively associated with the increase of amphetamine use disorder-related admission rates. In 2018, both ATS seized quantities and admission rates significantly increased, nearly doubling from the previous year. Rigorous, and multidisciplinary interventional studies to evaluate factors associated with increasing abuse of ATS should be a priority for policymakers and researchers in Saudi.


Assuntos
Estimulantes do Sistema Nervoso Central , Transtornos Relacionados ao Uso de Substâncias , Humanos , Anfetamina , Arábia Saudita/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Estimulantes do Sistema Nervoso Central/efeitos adversos , Convulsões
3.
Drug Alcohol Depend ; 243: 109740, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36608481

RESUMO

BACKGROUND: The opioid epidemic remains one of the most pressing public health crises facing the United States. Fentanyl and related synthetic opioid agonists have largely driven the rising rates of associated overdose deaths, in part, because of their surreptitious use as substitutes for other opioids and as adulterants in psychostimulants. Deaths involving opioids typically result from lethal respiratory depression, and it is currently unknown how co-use of psychostimulants with opioids affects respiratory toxicity. Considering psychostimulant overdoses have increased over 3-fold since 2013, and half of those co-involved opioids, this is a cardinal question. METHODS: Naloxone, d-amphetamine (AMPH), and (±)-methamphetamine (METH) were evaluated for their effects on basal and fentanyl-depressed respiration. Minute volume (MVb) was measured in awake, freely moving mice via whole-body plethysmography to quantify fentanyl-induced respiratory depression and its modulation by dose ranges of each test drug. RESULTS: Naloxone immediately reversed respiratory depression induced by fentanyl only at the highest dose tested (10 mg/kg). Both AMPH and METH exhibited bidirectional effects on MVb under basal conditions, producing significant (p ≤ 0.05) depressions then elevations of respiration as dose increased. Under depressed conditions the bidirectional effects of AMPH and METH on respiration were exaggerated, exacerbating and then reversing fentanyl-induced depression as dose increased. CONCLUSIONS: These results indicate that co-use of amphetamines with fentanyl may worsen respiratory depression, but conversely, monoaminergic components of the amphetamines may possibly be exploited to mitigate fentanyl overdose.


Assuntos
Estimulantes do Sistema Nervoso Central , Overdose de Drogas , Metanfetamina , Insuficiência Respiratória , Camundongos , Estados Unidos , Animais , Fentanila , Analgésicos Opioides/uso terapêutico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Naloxona/farmacologia , Naloxona/uso terapêutico , Metanfetamina/efeitos adversos , Overdose de Drogas/tratamento farmacológico , Anfetamina/efeitos adversos , Insuficiência Respiratória/induzido quimicamente , Respiração
4.
Psychopharmacology (Berl) ; 240(1): 227-237, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36544054

RESUMO

RATIONALE: Exposure to rewards can alter behavioral reactivity to them. For example, stimulants sensitize locomotor activation, whereas sexual experience sensitizes copulatory behaviors. Moreover, rewards can cross-sensitize one another. Although stimulants are known to cross-sensitize locomotor effects, the evidence for cross-sensitization between stimulants and sex is less clear. OBJECTIVES: This study determined the effects of single and repeated pre-exposure to methylphenidate (MPH) or sex on one another in adult male rats. METHODS: Cross-sensitization between MPH (5 mg/kg) and sex (30 min with sexually experienced female) was examined. Adult male rats were pre-exposed to 0, 1, or 10 trials of either sex or MPH before being exposed to the other reward. Locomotor chambers were used in MPH trials. Bilevel chambers were used in sexual trials, and sexual behaviors were video scored. RESULTS: The amount of prior sexual experience differentially influenced the ceiling of MPH-dependent sensitization; in the last drug trial, locomotion was highest in males given 1 previous sexual trial compared with 0 or 10. Compared with MPH-naive males, pre-exposure to MPH (1 and 10 trials) reduced the number of ejaculations without impacting sexual performance (intromission/mount latency and frequency). CONCLUSIONS: These findings indicate that the degree of pre-exposure to a reward can differentially affect reactivity to novel rewards. The results showed that previous findings of cross-sensitization between amphetamine and sex do not extend to MPH. However, exposure to MPH prior to sexual experience can increase the amount of sexual stimulation needed to achieve ejaculation.


Assuntos
Estimulantes do Sistema Nervoso Central , Metilfenidato , Ratos , Masculino , Feminino , Animais , Metilfenidato/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Anfetamina/farmacologia , Copulação
5.
Behav Brain Res ; 438: 114178, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36341913

RESUMO

Psychostimulants such as methylphenidate (MPD) and amphetamine (AMP) are often prescribed to young children and adolescents to treat behavioral disorders, or used to improve their intellectual performance in our competitive society. This is concerning as the temporal effects of how MPD exposure at a young age influences the response to MPD and AMP administration later in adulthood remains unclear. The objective of this study was to test whether MPD has the characteristics of substances that elicit behavioral symptoms of dependence and whether those effects are influenced by the initial age of MPD exposure. Three control and nine experimental groups of male rats were used. They were exposed to repetitive (chronic) 0.6, 2.5, or 10.0 mg/kg MPD in adolescence only, adulthood only, or adolescence and adulthood respectively. Then all groups were subsequently re-challenged with a single AMP dose in adulthood to test whether cross-sensitization between MPD and AMP was expressed, potentially as a result of prior MPD consumption. Exposure to 2.5 mg/kg and 10.0 mg/kg MPD in adolescence and adulthood or in adulthood alone led to cross-sensitization with AMP while exposure to 0.6 mg/kg MPD in adolescence and adulthood or in adulthood alone did not lead to cross-sensitization with AMP. Thus, these results indicate that MPD cross-sensitization with AMP is dose dependent.


Assuntos
Estimulantes do Sistema Nervoso Central , Metilfenidato , Animais , Masculino , Ratos , Anfetamina/farmacologia , Comportamento Animal , Estimulantes do Sistema Nervoso Central/farmacologia , Relação Dose-Resposta a Droga , Metilfenidato/farmacologia , Atividade Motora/fisiologia , Ratos Sprague-Dawley
6.
Addict Behav ; 138: 107567, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36521424

RESUMO

BACKGROUND: Psychostimulants (e.g., cocaine, amphetamine) are among the most widely used drugs globally with detrimental short and long-term physical, psychological and social consequences. There is limited data on psychostimulant use for various racial and ethnic groups, including Black people, and the challenges they face living as minorities overcoming historical challenges including increased incarceration associated with drug possession. METHODS: Peer-reviewed articles were identified in five databases (APA PsycInfo, CINAHL, Cochrane CENTRAL, Embase, MEDLINE). Eligible studies were published in French or English, provided empiral data on psychostimulant use in Black individuals living in a minority context. The PRISMA guideline was used for structuring the review. Random-effects meta-analyses were generated to estimate the pooled prevalence of lifetime and periodic psychostimulant use among Black individuals using STATA 16. RESULTS: Sixty-three studies published from 1991 to 2022 with a sample size of 139,683 Black individuals were included in the current meta-analysis. Results indicate a pooled prevalence estimate of 11.4% for any form of psychostimulant use among Black individuals. The pooled prevalence estimates were 12.4% (95% CI, 8.4% - 16.4%) for cocaine, 8.3% (95% CI, 0% - 19.1%) for amphetamines, and 11.4% (95% CI, 4.6% - 18.1%) for other stimulants. Prediction intervals for all psychostimulant types were highly heterogenous ranging from 0% to as high as 51.2% for amphetamine suggesting prevalence of use in some studies of Black people could be found to be as low as zero. Subgroup analyses were conducted to examine differences between age groups, gender, reference period, and type of assessment. CONCLUSIONS: High prevalence rates of psychostimulant use among Black people argues for greater access to evidence-based treatments. However, current psychosocial interventions are suboptimal, warranting further study. Consideration needs to be given to the challenges of the large range of prediction intervals, living in urban areas, racial discrimination experiences, race-based stress, and sociodemographic characteristics, including poverty, education level, age, gender.


Assuntos
Estimulantes do Sistema Nervoso Central , Cocaína , Humanos , Prevalência , Anfetamina , Fatores de Risco
7.
J Chromatogr A ; 1688: 463738, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36574747

RESUMO

Determination of amphetamine-type drugs (ATSs) in urine and wastewater is a simplified approach for the widespread monitoring of ATSs abuse. To improve the sensitivity of the analytical methods, molecularly imprinted polymers (MIPs) based solid-phase extraction (SPE) pretreatment attracted great attention in this field. Generally, smaller particle sizes and more uniform morphology of the MIPs could provide higher detection sensitivity. Our previous works showed reflux precipitation polymerization (RPP) is a method for synthesizing monodispersed MIPs with small particle size. However, synthesis of uniform spherical MIPs towards a group of targets has never been reported. Therefore, in the present work, MIPs towards a group of ATSs were synthesized via RPP with a pseudo template for the first time. After screening potential pseudo-templates, N-methylphenylethylamine (MPEA) was selected as the optimal pseudo-template. MPEA-MIPs were characterized by scanning electron microscope (SEM), FT-IR spectroscopy and X-ray photoelectron spectroscopy (XPS) spectra. Adsorption isotherms, adsorption kinetics and selectivity were evaluated, and the experimental results indicated that the MPEA-MIPs possessed good selectivity and adsorption property towards ATSs. After optimization of the MIP-SPE procedure, the MIP-SPE cartridges were then coupled with liquid chromatography and tandem mass spectrometry (LC-MS/MS) for determination of ATSs. The evaluation results showed that MIP-SPE-LC-MS/MS displayed good linearity (R2 >0.991) in the linear range (1.0-50.0 µg/L for urine and 0.5-50.0 µg/L for wastewater), and low matrix effect (85-112%). The limit of detection (LOD) was 0.05 -0.29 µg/L, and the accuracy (85-115%) and repeatability (RSD ≤ 15%) were satisfactory at low, medium and high concentrations. To the best of our knowledge, this is the first time that dummy MIPs towards a group of ATSs were synthesized by RPP polymerization, which showed great potential for the detection of ATSs in urine and wastewater.


Assuntos
Estimulantes do Sistema Nervoso Central , Impressão Molecular , Anfetamina , Cromatografia Líquida , Polímeros Molecularmente Impressos , Polimerização , Espectroscopia de Infravermelho com Transformada de Fourier , Polímeros/química , Espectrometria de Massas em Tandem/métodos , Extração em Fase Sólida/métodos , Impressão Molecular/métodos , Adsorção , Cromatografia Líquida de Alta Pressão/métodos
8.
Neuropharmacology ; 225: 109387, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36567004

RESUMO

The function of the dopamine transporter (DAT) is regulated by membrane cholesterol content. A direct, acute removal of membrane cholesterol by methyl-ß-cyclodextrin (MßCD) has been shown to reduce dopamine (DA) uptake and release mediated by the DAT. This is of particular interest because a few widely prescribed statins that lower peripheral cholesterol levels are blood-brain barrier (BBB) penetrants, and therefore could alter DAT function through brain cholesterol modulation. The goal of this study was to investigate the effects of prolonged atorvastatin treatment (24 h) on DAT function in neuroblastoma 2A cells stably expressing DAT. We found that atorvastatin treatment effectively lowered membrane cholesterol content in a concentration-dependent manner. Moreover, atorvastatin treatment markedly reduced DA uptake and abolished cocaine inhibition of DA uptake, independent of surface DAT levels. These deficits induced by atorvastatin treatment were reversed by cholesterol replenishment. However, atorvastatin treatment did not change amphetamine (AMPH)-induced DA efflux. This is in contrast to a small but significant reduction in DA efflux induced by acute depletion of membrane cholesterol using MßCD. This discrepancy may involve differential changes in membrane lipid composition resulting from chronic and acute cholesterol depletion. Our data suggest that the outward-facing conformation of DAT, which favors the binding of DAT blockers such as cocaine, is more sensitive to atorvastatin-induced cholesterol depletion than the inward-facing conformation, which favors the binding of DAT substrates such as AMPH. Our study on statin-DAT interactions may have clinical implications in our understanding of neurological side effects associated with chronic use of BBB penetrant statins.


Assuntos
Cocaína , Inibidores de Hidroximetilglutaril-CoA Redutases , Anfetamina/farmacologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Cocaína/farmacologia , Dopamina/metabolismo , Atorvastatina/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Colesterol/metabolismo
9.
Forensic Toxicol ; 40(2): 383-392, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36454420

RESUMO

PURPOSE: Death related to the use of drugs is evident when drugs are detected in biological matrices within toxic levels, but sometimes it can be less obvious. Intoxications after 2,5-dimethoxy-4-chloroamphetamine (DOC) use are occurring but up to date, only one fatality has been reported. Here we present the case of a young woman admitted to hospital as she presented vomiting, convulsions and cardiorespiratory arrest. METHODS: Blood ethanol concentration was determined using gas chromatography with flame ionization detection and toxicological screenings (blood, gastric content and hair samples) were performed using liquid chromatography with diode array detection, gas chromatography or liquid chromatography with mass spectrometry detection. RESULTS: Her health state declined with cardiac troubles, organs failure and cerebral edema till death occurring 4 days later. The autopsy revealed the presence of hemorrhagic infiltration inside the left ventricle, pulmonary edema and hemorrhagic infiltration of the terminal ileum. The analysis of biological fluids confirmed the presence of DOC (< 10 ng/mL in cardiac blood sample), buprenorphine, cocaine and cannabis metabolites. The analysis of hair highlighted a history of drugs abuse. CONCLUSION: In the absence of evident identified cause, the hypothesis of a death due to acute drugs use within a history of chronic consumption of drugs has been put forward. The concentration of some substances such as new psychoactive substances can be low in biological matrices but the toxic effects can be additive and lead to death even within young people, hence the importance of the knowledge of consumption history.


Assuntos
Anfetamina , Morte Encefálica , Humanos , Feminino , Adolescente , Cromatografia Gasosa-Espectrometria de Massas , Ionização de Chama , Cromatografia Líquida
10.
BMC Psychiatry ; 22(1): 815, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36544132

RESUMO

BACKGROUND: Depression is a mental health problem and substance use concerns are socially unacceptable behaviors. While depression and substance use may individually impact self-concept and social relationships, their co-occurrence can increase the risk of self-stigmatization. However, there is no evidence regarding how depression and self-stigma may influence each other over time. The aim of the current study was to evaluate the cross-sectional and longitudinal relationships between features of depression and self-stigma in people with substance use disorders. METHODS: Overall, 319 individuals with substance use disorders (273 males) with a mean (± SD) age of 42.2 (± 8.9) years were recruited from a psychiatric center in Taiwan by convenience sampling. They were assessed for features of depression and self-stigma at four times over a period of nine months using the depression subscale of the Depression Anxiety Stress Scales (DASS-21) and Self-Stigma Scale-Short S (SSS-S), respectively. Repeated-measures analyses of variance, Pearson correlations and cross-lagged models using structural equation modeling examined cross-sectional and temporal associations between depression and self-stigma. RESULTS: Positive cross-sectional associations were found between depressive features and all assessed forms of self-stigma over time (0.13 < r < 0.92). Three models of cross-lagged associations between different forms of self-stigma and depressive features indicated good fit indices (comparative fit index > 0.98). The direction of associations between depressive features towards self-stigma was stronger than the opposite direction. CONCLUSION: Positive associations between depressive features and self-stigma were found in people with substance use disorders. Although these associations may be bidirectional longitudinally, the directions from depressive features to self-stigma may be stronger than the reverse directions, suggesting treatment of depression in earlier stages may prevent self-stigmatization and subsequent poor outcomes in people with substance use disorders.


Assuntos
Heroína , Transtornos Relacionados ao Uso de Substâncias , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Anfetamina , Estudos Transversais , Estigma Social , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/psicologia , Depressão/psicologia
11.
Int J Mol Sci ; 23(24)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36555568

RESUMO

Schizophrenia is a chronic mental illness, which remains difficult to treat. A high resistance to the available therapies, their insufficient efficacy, and numerous side effects are the reasons why there is an urgent need to develop new antipsychotics. This study aimed to assess the antipsychotic-like effects of JJGW08, a novel arylpiperazine alkyl derivative of salicylamide, in rodents. First, considering the JJGW08 receptor profile, we investigated the compound's intrinsic activity towards dopamine D2 and serotonin 5-HT1A, 5-HT2A, and 5-HT7 receptors using functional assays. Next, we assessed the effect of JJGW08 on MK-801- and amphetamine-induced hyperlocomotion, its risk of inducing catalepsy and impairing motor coordination, as well as the anxiolytic-like effects in the four-plate and marble burying tests in mice. Finally, we investigated the antipsychotic-like properties of JJGW08 in rats using MK-801-induced hyperlocomotion and prepulse inhibition tests. We found that JJGW08 showed antagonistic properties at dopamine D2 and serotonin 5-HT1A, 5-HT2A, and 5-HT7 receptors. However, the effect on the 5-HT2A and 5-HT7 receptors was very weak. Moreover, the tested compound showed an antipsychotic-like effect in MK-801- and amphetamine-induced hyperlocomotion but not in a prepulse inhibition test in rats. Notably, JJGW08 demonstrated anxiolytic-like properties in both behavioral tests. Importantly, the compound did not induce catalepsy or motor coordination impairment in mice at antipsychotic-like doses. Our study suggests it is worth searching for new potential antipsychotics among arylpiperazine alkyl derivatives of salicylamide.


Assuntos
Ansiolíticos , Antipsicóticos , Ratos , Camundongos , Animais , Antipsicóticos/efeitos adversos , Serotonina/efeitos adversos , Ansiolíticos/farmacologia , Dopamina/efeitos adversos , Roedores , Maleato de Dizocilpina/efeitos adversos , Catalepsia/induzido quimicamente , Catalepsia/tratamento farmacológico , Anfetamina/farmacologia
12.
Int J Mol Sci ; 23(24)2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36555273

RESUMO

Microinjection of cocaine- and amphetamine-regulated transcript (CART) peptide 55-102 into the nucleus accumbens (NAcc) core significantly attenuates psychostimulant-induced locomotor activity. However, the molecular mechanism remains poorly understood. We examined the phosphorylation levels of Akt, glycogen synthase kinase 3ß (GSK3ß), and glutamate receptor 1 (GluA1) in NAcc core tissues obtained 60 min after microinjection of CART peptide 55-102 into this site, followed by systemic injection of amphetamine (AMPH). Phosphorylation levels of Akt at Thr308 and GSK3ß at Ser9 were decreased, while those of GluA1 at Ser845 were increased, by AMPH treatment. These effects returned to basal levels following treatment with CART peptide 55-102. Furthermore, the negative regulatory effects of the CART peptide on AMPH-induced changes in phosphorylation levels and locomotor activity were all abolished by pretreatment with the S9 peptide, an artificially synthesized indirect GSK3ß activator. These results suggest that the CART peptide 55-102 in the NAcc core plays a negative regulatory role in AMPH-induced locomotor activity by normalizing the changes in phosphorylation levels of Akt-GSK3ß, and subsequently GluA1 modified by AMPH at this site. The present findings are the first to reveal GSK3ß as a key regulator of the inhibitory role of the CART peptide in psychomotor stimulant-induced locomotor activity.


Assuntos
Anfetamina , Glicogênio Sintase Quinase 3 beta , Atividade Motora , Proteínas do Tecido Nervoso , Animais , Ratos , Anfetamina/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Núcleo Accumbens , Peptídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt , Ratos Sprague-Dawley , Proteínas do Tecido Nervoso/metabolismo
13.
Front Public Health ; 10: 998768, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388362

RESUMO

Background: Amphetamine-type stimulants (ATS) use has become popular in China. This study explored ATS use status and related risk factors of hepatitis C virus (HCV) infection among ATS users in Jinghong City, Xishuangbanna Prefecture, Yunnan Province, China. Methods: A cross-sectional study was conducted by questionnaires from January to July 2021 in border area in Yunnan. Respondent driving sampling and consecutive sampling was carried out among border drug users, and blood samples were tested for HCV antibodies. HCV infection and related risk factors among ATS users were measured. Descriptive, univariate and multivariate analysis were conducted separately by Software SPSS 26.0. Results: The ATS users accounted for 85.82% (345/402) among drug users, while anti-HCV antibody prevalence was 6.38% (22/345) among ATS users. The combined use of other types of drugs (OR = 7.29, 95%CI: 1.982-26.81, P = 0.003), injection drug use (OR = 6.823, 95%CI: 1.898-24.525, P = 0.003), average monthly income (OR = 4.825, 95%CI: 1.325-17.566, P = 0.017) might increase the risk of HCV infection among ATS users. ATS users with high school or above had higher HCV infection rates than those with primary school or below (OR = 5.718, 95%CI: 1.172-27.908, P = 0.031). Conclusion: Taken together, among drug users using ATS in Jinghong City, Xishuangbanna Autonomous Prefecture, Yunnan Province, combined use of multiple drugs and intravenous drug use was the high risk factor for HCV infection. Therefore, corresponding education and intervention measures should be taken.


Assuntos
Usuários de Drogas , Hepatite C , Humanos , Anfetamina , Estudos Transversais , China/epidemiologia , Hepatite C/epidemiologia , Hepacivirus , Fatores Econômicos
14.
Pharmacol Biochem Behav ; 221: 173489, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36375621

RESUMO

In vulnerable consumers, the first drug exposure induces various neurobehavioral adaptations that may represent the starting point toward addiction. Elucidating the neuroplastic mechanisms underlying that first rewarding experience would contribute to understanding the transition from recreational to compulsive drug use. In a preclinical model with juvenile rats, we analyzed the time-dependent fluctuations in the expression of neuroplasticity-related genes like the brain-derived neurotrophic factor (BDNF), its tropomyosin receptor kinase B (TrkB), the cAMP response element-binding protein (CREB), the microRNA-132, the Rho GTPase-activating protein 32 (p250GAP), the corticotropin-releasing factor (CRF), and the neurotransmitters contents in the nucleus accumbens (NAc) and the dorsal striatum (DS) 45, 90, and 180 min after an amphetamine (AMPH) injection. As expected, AMPH altered the concentration of norepinephrine, dopamine, DOPAC, and serotonin in a region- and time-dependent manner. Regarding gene expression, AMPH at 45 min upregulated BDNF and primiR-132 expression in NAc and downregulated TrkB expression in DS. At 90 min, AMPH upregulated TrkB, CREB, p250GAP, and primiR-132 expression in NAc and BDNF, primiR-132, and CRF in DS. At 180 min, only BNDF in NAc continued to be upregulated by AMPH. Based on the levels of AMPH-induced hyperactivity, we classified the rats as low and high AMPH responders. High AMPH responders characterized by overexpressing BDNF, CREB, p250GAP, and CRF in NAc and by showing lower levels of dopamine and serotonin metabolites and turnovers in both regions. Our findings demonstrated that a single AMPH administration is enough to induce neuroplastic adaptations, especially in the NAc of prone rats.


Assuntos
Estimulantes do Sistema Nervoso Central , MicroRNAs , Ratos , Animais , Anfetamina/farmacologia , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Dopamina/metabolismo , Hormônio Liberador da Corticotropina , Serotonina/metabolismo , Ratos Sprague-Dawley , Núcleo Accumbens/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , MicroRNAs/metabolismo
15.
J Am Assoc Lab Anim Sci ; 61(6): 615-623, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36328417

RESUMO

Changes in housing density, including individual housing, are commonly necessary in animal research. Obtaining reproducibility and translational validity in biomedical research requires an understanding of how animals adapt to changes in housing density. Existing literature mainly addresses acclimatization after transportation. We used a within-subject design to examine changes in behavior and weight gain of 4-mo-old male Wistar Han rats after reduction of their social group (RSG; due to removal of one rat from a cage containing 3 rats) and social isolation (SI; the removed rat) for the subsequent 2 wk. Changes in weight gain and in exploratory and center-avoidance behavior in an inescapable open arena (OA) were measured before (D0) and on days 7 and 14 (D7 and D14, respectively) after social change. The motor response to d-amphetamine (1.5 mg/kg), which stimulates behavioral arousal in response to novelty, was assessed at D14. Within-subject design revealed that RSG rats in OA had less locomotion at D7 but not more center-avoidance behavior and had returned to the D0 activity level at D14; SI rats in OA had consistently less locomotion and more center-avoidance behavior. Rearing behavior during OA exposure did not change in either group. However, SI rats showed more center-avoidance behavior in OA, greater weight gain, and less amphetamine-induced rearing at D14 as compared with RSG rats. These data indicate that after RSG, mature adult male rats require 2 wk to return to their baseline level of OA-related behavior, while after SI they gain weight and acquire maladaptive exploratory and center-avoidance behavior. The finding that SI produces maladaptive behavioral and physiologic alterations in adult male rats deserves attention because these changes could have confounding effects on research findings.


Assuntos
Anfetamina , Isolamento Social , Animais , Ratos , Masculino , Ratos Wistar , Reprodutibilidade dos Testes , Anfetamina/farmacologia , Aumento de Peso , Peso Corporal , Comportamento Exploratório , Comportamento Social , Comportamento Animal
16.
Adv Clin Chem ; 111: 217-263, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36427911

RESUMO

Traditional clinical toxicology involves the analysis of patient urine samples by immunoassays designed to detect opiates/opioids, amphetamine/methamphetamine, benzodiazepines, barbiturates, cocaine metabolite and tetrahydrocannabinol. Expanded drug screens may also include assays for oxycodone, buprenorphine, methadone, 6-monoacetylmorphine, phencyclidine and fentanyl. Patient samples that are positive are commonly reflexed to be run on a liquid chromatography-tandem mass spectrometry confirmatory assay, as are samples that are negative for drugs that are prescribed to the patient. These mass spectrometry assays are targeted and so only detect the drugs or drug metabolites that they were designed to detect. With the explosion of new psychoactive substances in the past decade, it has become necessary for clinical laboratories to reevaluate traditional targeted drug screening approaches. The utility of high-resolution mass spectrometry in this arena has been recognized and this review will discuss the traditional approach to, and the recent advances in clinical toxicology including data collection and interrogation strategies for new psychoactive substances using high-resolution mass spectrometry (HRMS). Various modes of data processing techniques including targeted analysis, suspect screening and non-targeted analysis will also be described using HRMS. Several published methods will be described to demonstrate the utility of various data acquisition and processing techniques using HRMS in NPS analysis specifically.


Assuntos
Dronabinol , Detecção do Abuso de Substâncias , Humanos , Espectrometria de Massas , Metadona , Anfetamina
17.
Pharmacol Biochem Behav ; 221: 173483, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36270348

RESUMO

The rewarding effects of psychostimulants appear to be distinct between dominant and subordinate individuals. In turn, the endocannabinoid system is an important modulator of drug reward in the nucleus accumbens and medial prefrontal cortex, however the connection with social dominance is yet to be established. Male rats were classified as dominant or subordinate on the basis of their spontaneous agonistic interactions and drug reward was assessed by means of conditioned place preference with amphetamine (AMPH). In addition, the expression of CB1R, CB2R, FAAH1, and DAGLa was quantified from accumbal and cortical tissue samples. Our findings demonstrate that dominant rats required a lesser dose of AMPH to acquire a preference for the drug-associated compartment, thereby suggesting a higher sensitivity to the rewarding effects of AMPH. Furthermore, dominants exhibited a lower expression of CB1R in the medial prefrontal cortex and nucleus accumbens. This study illustrates how CBR1 expression could differentiate the behavioral phenotypes associated to social dominance.


Assuntos
Anfetamina , Estimulantes do Sistema Nervoso Central , Masculino , Ratos , Animais , Anfetamina/farmacologia , Recompensa , Núcleo Accumbens/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , Estimulantes do Sistema Nervoso Central/metabolismo , Receptores de Canabinoides/metabolismo
18.
Water Res ; 225: 119182, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36215836

RESUMO

Consumption of amphetamine and methamphetamine, two common illicit drugs, has been monitored by wastewater-based epidemiology (WBE) in many countries over the past decade. There is potential for the estimated amount of amphetamine used to be skewed at locations where methamphetamine is also consumed, because amphetamine is also excreted to wastewater following methamphetamine consumption. The present study aims to review the available data in the literature to identify an average ratio of amphetamine/methamphetamine (AMP/METH) that is excreted to wastewater after methamphetamine consumption. This ratio could then be used to refine the estimation of amphetamine consumption in catchments where there is both amphetamine and methamphetamine use. Using data from more than 6000 wastewater samples from Australia where methamphetamine is the dominant illicit amphetamine-type substance on the market, we were able to subtract the contribution of legal sources of amphetamine contribution and obtain the median AMP/METH ratio in wastewater of 0.09. Using this value, the amphetamine derived from methamphetamine consumption can be calculated and subtracted from the total amphetamine mass loads in wastewater samples. Without considering the contribution of amphetamine from methamphetamine use, selected European catchments with comparable consumption of amphetamine and methamphetamine showed up to 83% overestimation of amphetamine use. For catchments with AMP/METH ratio greater than 1.00, the impact of amphetamine from methamphetamine would be negligible; for catchments with AMP/METH ratio in the range of 0.04-0.19, it will be difficult to accurately estimate amphetamine consumption.


Assuntos
Drogas Ilícitas , Metanfetamina , Poluentes Químicos da Água , Anfetamina , Vigilância Epidemiológica Baseada em Águas Residuárias , Detecção do Abuso de Substâncias , Monofosfato de Adenosina , Poluentes Químicos da Água/análise
19.
Psychopharmacology (Berl) ; 239(11): 3723-3730, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36190536

RESUMO

RATIONALE: Synthetic phenethylamine (PEA) analogs, such as ß-methylphenethylamine (BMPEA) and N,α-diethylphenethylamine (DEPEA), are often found in dietary supplements, despite regulations prohibiting their sale. PEA analogs are structurally related to amphetamine, and we have shown that BMPEA and DEPEA produce cardiovascular stimulation mimicking the effects of amphetamine. However, few studies have examined behavioral effects of BMPEA, DEPEA, and other PEA analogs. OBJECTIVES: Here, we examined the reinforcing effects of α-ethylphenethylamine (AEPEA, 1 mg/kg/injection), DEPEA (1 mg/kg/injection), and BMPEA (3 mg/kg/injection) as compared to amphetamine (0.1 mg/kg/injection) using a fixed-ratio 1 self-administration paradigm in male rats. METHODS: Male rats were trained in self-administration chambers containing 2 nose-poke holes. A nose-poke response in the active hole delivered drug or saline, whereas a nose-poke response in the inactive hole had no programmed consequence. Four groups of rats were initially trained for 10 days with the doses noted above. Upon acquisition of drug self-administration, a dose-effect function was determined by training rats on 3 additional doses for 3 days each. A separate group of rats was trained with saline. RESULTS: Male rats self-administered each PEA analog and amphetamine, as shown by significant increases in active responses versus inactive responses. Subsequent dose-response testing showed clear differences in potency of the compounds. Amphetamine showed a typical inverted U-shaped dose-effect function, peaking at 0.1 mg/kg/injection. AEPEA and DEPEA also showed inverted dose-effect functions, with each peaking at 0.3 mg/kg/injection. BMPEA did not show an inverted U-shaped dose-effect function, but active responding slowly increased up to a dose of 6 mg/kg/injection. CONCLUSIONS: Taken together, our findings indicate that dietary supplements containing PEA analogs may have significant abuse liability when used recreationally.


Assuntos
Anfetamina , Fenetilaminas , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Anfetamina/farmacologia , Fenetilaminas/farmacologia , Autoadministração , Suplementos Nutricionais , Relação Dose-Resposta a Droga
20.
Biosensors (Basel) ; 12(9)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36140096

RESUMO

Abuse of illicit drugs has become a major issue of global concern. As a synthetic amphetamine analog, 3,4-Methylene Dioxy Amphetamine (MDA) causes serotonergic neurotoxicity, posing a serious risk to human health. In this work, a two-dimensional substrate of ITO/Au is fabricated by transferring Au nanoparticle film onto indium-tin oxide glass (ITO). By magnetic inducing assembly of Fe3O4@Au onto ITO/Au, a sandwich-based, surface-enhanced Raman scattering (SERS) detection strategy is designed. Through the use of an external magnet, the MDA is retained in the region of hot spots formed between Fe3O4@Au and ITO/Au; as a result, the SERS sensitivity for MDA is superior compared to other methods, lowering the limit of detection (LOD) to 0.0685 ng/mL and attaining a corresponding linear dynamic detection range of 5-105 ng/mL. As an actual application, this magnetically improved SERS sensing strategy is successfully applied to distinguish MDA in urine at trace level, which is beneficial to clinical and forensic monitors.


Assuntos
Drogas Ilícitas , Nanopartículas Metálicas , Anfetamina , Ouro , Humanos , Índio , Análise Espectral Raman/métodos , Compostos de Estanho
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