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1.
Talanta ; 237: 122904, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736717

RESUMO

In this work, we have focused on the profiling of 5647 street samples covering marijuana, common and new recreational illicit drugs. All samples were analyzed using gas chromatography-mass spectrometry (GC-MS) technique. In total we have identified 53 illicit drugs with Δ-9-tetrahydrocannabinol (THC), amphetamine, N-ethylhexedrone, 3,4-methylenedioxy methamphetamine (MDMA), 4-chloromethcathinone (4-CMC), α-pyrrolidinoisohexaphenone (α-PHiP), cocaine, and 4-chloroethcathinone (4-CEC) being most commonly found and making 38.5, 17.8, 15.5, 8.0, 3.5, 2.7, 2.1, and 2.0% of the total studied pool, respectively. Except for methadone, all analyzed street samples were spiked with at least one cutting agent. Caffeine was the most frequently found adulterating addition present in around 33% (excluding marijuana) of the analyzed samples. Other identified cutting agents make an impressive group of more than 160 compounds. Finally, we have tabulated, illustrated, and discussed presented data in a view of smart and portable sensors development.


Assuntos
Cocaína , Drogas Ilícitas , Metanfetamina , Anfetamina/análise , Cocaína/análise , Cromatografia Gasosa-Espectrometria de Massas , Metanfetamina/análise , Detecção do Abuso de Substâncias
2.
Fa Yi Xue Za Zhi ; 37(4): 561-568, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34726012

RESUMO

Abstract: Synthetic cathinones are a class of new psychoactive substances with a structure similar to amphetamine drugs, which can produce excitatory effects similar to drugs such as amphetamine and cocaine after being taken. In recent years, the abuse of synthetic cathinones worldwide has become increasingly serious, posing a serious threat to social security and public health. This article focuses on several common synthetic cathinones, collects their research results in animal autonomous activity experiments and drug dependence model experiments and summarizes their relevant experimental conclusions in animal body temperature regulation, learning and memory, and anxiety, in order to provide data reference and method guidance for the domestic development of related drug research.


Assuntos
Alcaloides , Drogas Ilícitas , Alcaloides/farmacologia , Anfetamina , Animais , Comportamento Animal
3.
Water Res ; 206: 117719, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34624656

RESUMO

Amphetamine (AMP), methamphetamine (MAMP) and 3,4-methylenedioxymethamphetamine (MDMA) occur in wastewater not only as a result of illicit consumption, but also, in some cases, from prescription drug use or by direct drug disposal into the sewage system. Enantiomeric profiling of these chiral drugs could give more insight into the origin of their occurrence. In this manuscript, a new analytical methodology for the enantiomeric analysis of amphetamine-like substances in wastewater has been developed. The method consists of a solid-phase extraction (SPE) followed by liquid chromatography-triple quadrupole-tandem mass spectrometry (LC-MS/MS), which showed low quantification limits in the 2.4-5.5 ng L-1 range. The LC-MS/MS method was first applied to characterize a total of 38 solid street drug samples anonymously provided by consumers. The results of these analysis showed that AMP and MDMA trafficked into Spain are synthesized as racemate, while MAMP is exclusively produced as the S(+)-enantiomer. Then, the analytical method was employed to analyse urban wastewater samples collected from the wastewater treatment plants (WWTPs) of five different cities in 2018 and 2019. Consumption estimated through normalized population loads in wastewater showed an increased pattern of AMP use in the Basque Country. Furthermore, the enantiomeric profiling of wastewater samples was contrasted to lisdexamfetamine (LIS) and selegiline (SEL) prescription figures, two pharmaceuticals which metabolize to S(+)-AMP, and to R(-)-AMP and R(-)-MAMP, respectively. From this analysis, and considering uncertainties derived from metabolism and adherence to treatment, it was concluded that LIS is a relevant source of AMP in those cases with low wastewater loads, i.e. up to a maximum of 60% of AMP detected in wastewater in some samples could originate from LIS prescription, while SEL does not represent a significant source of AMP nor MAMP. Finally, removal efficiencies could be evaluated for the WWTP (serving ca. 860,000 inhabitants) with higher AMP influent concentrations. The removal of AMP was satisfactory with rates higher than 99%, whereas MDMA showed an average removal of approximately 60%, accompanied by an enrichment of R(-)-MDMA.


Assuntos
Águas Residuárias , Poluentes Químicos da Água , Anfetamina , Cromatografia Líquida , Espectrometria de Massas em Tandem , Poluentes Químicos da Água/análise
4.
Eur J Neurosci ; 54(7): 6382-6396, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34481424

RESUMO

Overdose death rates caused by psychostimulants have increased by 22.3% annually from 2008 to 2017. Cue-evoked drug craving progressively increases and contributes to perpetual relapse. Preclinical models have determined that glutamate receptor plasticity within the nucleus accumbens (NAc) drives amplified cue-evoked drug seeking after prolonged abstinence (>40 days). Isolated condition (IC) rearing increases cocaine and amphetamine (AMP) self-administration and cue-induced reinstatement. We tested the hypothesis that housing in the IC will augment AMP seeking after short and prolonged abstinence from AMP self-administration when compared with rats reared in the enrichment condition (EC). EC and IC male rats acquired stable AMP or SAL self-administration and were tested in a cue-induced AMP-seeking test after 1 and 40 days of abstinence. After the seeking test, the whole NAc was extracted and prepared for western blot analysis. Results indicate that IC rats had more active lever presses during a brief extinction interval and during the cue-induced seeking test. After 40 days of abstinence, IC rats had more active lever presses than EC rats during the cue-induced seeking test. Western blots indicated that the expression ratio between GluA1:mGlur5 was reduced only in IC-AMP-trained rats and the ratio between GluA1:mGlur1 was positively correlated with AMP seeking after prolonged abstinence in IC-AMP rats. These results indicate that IC housing engenders a vulnerable phenotype prone to persistent AMP seeking. The behavioural momentum of this vulnerable phenotype is further revealed when AMP-associated cues are presented following prolonged abstinence.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Anfetamina , Animais , Sinais (Psicologia) , Comportamento de Procura de Droga , Extinção Psicológica , Habitação , Masculino , Núcleo Accumbens , Ratos , Autoadministração
5.
Lakartidningen ; 1182021 09 13.
Artigo em Sueco | MEDLINE | ID: mdl-34515329

RESUMO

Workplace alcohol and drug testing is increasingly used at employment, for regular checks, and in case of accident, incident, or suspicion of drug exposure. The test results provide valuable objective information about drug use in the society. At the Karolinska University Laboratory (Stockholm, Sweden), the number of samples from drug testing in the workplace has quadrupled in the last decade. Almost all urine samples are tested for amphetamines (amphetamine, methamphetamine and MDMA), benzodiazepines (prescribed substances), cannabis, cocaine and opiates, and some also for alcohol (i.e. the metabolites ethyl glucuronide and ethyl sulfate) and drugs such as tramadol and oxycodone. The proportion of samples that test positive for one or more drugs has increased steadily in recent years to over 5%. Substances commonly detected are, in order of appearance, cannabis, amphetamines (amphetamine and MDMA), benzodiazepines, opiates (mainly codeine and only few due to heroin use), and cocaine. Other common substances are alcohol, tramadol, and oxycodone, but these are only tested for in a limited, and possibly selected, proportion of samples. After an MRO has reviewed the positive laboratory results, about 30% of cases are excluded mainly due to legal prescription as medicine. In 2020, the proportion of positive test results decreased, possibly due to reduced access to illicit drugs during the corona pandemic. In summary, results from drug testing in the workplace indicate that illicit use of drugs shows an increasing trend in Sweden.


Assuntos
Cocaína , Drogas Ilícitas , Transtornos Relacionados ao Uso de Substâncias , Anfetamina , Humanos , Detecção do Abuso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Suécia/epidemiologia , Local de Trabalho
6.
Transl Psychiatry ; 11(1): 427, 2021 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-34392304

RESUMO

Despite the high prevalence of obesity, little is known about its potential impact on the pharmacokinetics of psychotropic drugs. In the course of investigating the role of the microRNA system on neuronal signaling, we found that mice lacking the translin/trax microRNA-degrading enzyme display an exaggerated locomotor response to amphetamine. As these mice display robust adiposity in the context of normal body weight, we checked whether this phenotype might reflect elevated brain levels of amphetamine. To assess this hypothesis, we compared plasma and brain amphetamine levels of wild type and Tsn KO mice. Furthermore, we checked the effect of diet-induced increases in adiposity on plasma and brain amphetamine levels in wild type mice. Brain amphetamine levels were higher in Tsn KO mice than in wild type littermates and correlated with adiposity. Analysis of the effect of diet-induced increases in adiposity in wild type mice on brain amphetamine levels also demonstrated that brain amphetamine levels correlate with adiposity. Increased adiposity displayed by Tsn KO mice or by wild type mice fed a high-fat diet correlates with elevated brain amphetamine levels. As amphetamine and its analogues are widely used to treat attention deficit disorder, which is associated with obesity, further studies are warranted to assess the impact of adiposity on amphetamine levels in these patients.


Assuntos
Adiposidade , Anfetamina , Tecido Adiposo , Anfetamina/farmacologia , Animais , Encéfalo , Dieta Hiperlipídica , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade
7.
J Pharm Biomed Anal ; 205: 114317, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34419812

RESUMO

Amphetamine-type stimulants (ATS) like amphetamine ('speed'), methamphetamine ('crystal meth') and 3,4-methylenedioxy-N-methylamphetamine (MDMA, 'ecstasy') represent some of the most frequently abused drugs worldwide. Another less frequently abused ATS is 4-fluoroamphetamine (4-FA). The enantiomers of these four compounds exhibit different pharmacokinetic and pharmacodynamic properties. According to the free drug theory, the pharmacological properties of a substance are dependent on its plasma protein binding (PPB). However, data on PPB of stimulant enantiomers in humans are rare or non-existent. Human plasma samples were spiked with racemic mixtures of the stimulants and subjected to ultrafiltration to extract the unbound fraction. Enantioselective liquid chromatography - tandem mass spectrometry (LC-MS/MS) methods were applied using a chiral Phenomenex® Lux3 µm AMP column. Method validation showed satisfactory selectivity, linearity (0.5 250 ng/mL), accuracy and precision. Enantiomers were quantified before and after ultracentrifugation to determine PPB. For all analytes, low to medium plasma protein binding was found. For (R)-amphetamine a slightly but significantly higher PPB was found compared to the (S)-enantiomer (31.7 % vs 29.0 %). (R)-MDMA also showed only slightly but significantly significantly higher PPB than (S)-MDMA, although the mean difference was negligible (21.6 % vs 21.3 %). For the enantiomers of methamphetamine and 4-FA, no significant differences in PPB were found. In summary, there were no or only minor differences in PBB for the enantiomers of all investigated compounds. The different pharmacological properties of the stimulant enantiomers can therefore not be explained by differences in PPB.


Assuntos
Estimulantes do Sistema Nervoso Central , Drogas Ilícitas , Anfetamina , Cromatografia Líquida , Humanos , Ligação Proteica , Estereoisomerismo , Espectrometria de Massas em Tandem
8.
BMJ Case Rep ; 14(8)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34413029

RESUMO

Thyroid storm is a rare, life-threatening endocrine emergency with a high mortality rate of up to 30%. We present a unique management challenge of a critically ill patient who developed thyroid storm in the setting of a duodenal perforation from amphetamine-associated non-occlusive mesenteric ischaemia. The diagnosis of 'thyroid storm' was made based on clinical criteria and a Burch-Wartofsky score of 100. During emergent exploratory laparotomy, a 1 cm duodenal perforation with surrounding friable tissue was found and repaired. Intraoperatively, a nasogastric tube was guided distal to the area of perforation to allow for enteric administration of medications, which was critical in the setting of thyroid storm. Therapeutic plasma exchange achieved biochemical control of our patient's thyroid storm but ultimately did not prevent in-hospital mortality.


Assuntos
Úlcera Duodenal , Úlcera Péptica Perfurada , Crise Tireóidea , Anfetamina , Humanos , Isquemia/induzido quimicamente , Crise Tireóidea/complicações , Crise Tireóidea/tratamento farmacológico
9.
eNeuro ; 8(5)2021.
Artigo em Inglês | MEDLINE | ID: mdl-34462310

RESUMO

Psychostimulants such as amphetamine (AMPH) target dopamine (DA) neuron synapses to engender drug-induced plasticity. While DA neurons modulate the activity of striatal (Str) cholinergic interneurons (ChIs) with regional heterogeneity, how AMPH affects ChI activity has not been elucidated. Here, we applied quantitative fluorescence imaging approaches to map the dose-dependent effects of a single dose of AMPH on ChI activity at 2.5 and 24 h after injection across the mouse Str using the activity-dependent marker phosphorylated ribosomal protein S6 (p-rpS6240/244). AMPH did not affect the distribution or morphology of ChIs in any Str subregion. While AMPH at either dose had no effect on ChI activity after 2.5 h, ChI activity was dose dependently reduced after 24 h specifically in the ventral Str/nucleus accumbens (NAc), a critical site of psychostimulant action. AMPH at either dose did not affect the spontaneous firing of ChIs. Altogether this work demonstrates that a single dose of AMPH has delayed regionally heterogeneous effects on ChI activity, which most likely involves extra-Str synaptic input.


Assuntos
Anfetamina , Dopamina , Anfetamina/farmacologia , Animais , Colinérgicos , Interneurônios , Camundongos , Núcleo Accumbens
10.
Sci Total Environ ; 797: 149058, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34303256

RESUMO

The occurrence and levels of amphetamine like substances (ALSs) in various environments, as a group of illicit psychoactive substances, have attracted great attention due to their potential ecological risks. In this study, three ALSs (i.e., ephedrine (EPH), amphetamine (AMP) and methamphetamine (METH)) in the raw domestic wastewater (RDW) and surface river water (SRW) collected from the rural area in South China were analyzed. METH was identified as the prevalent and dominant ALS in the RDW, which was detected in approximately 99.0% of the samples with a mean concentration of 0.7 µg·L-1, followed by AMP and EPH. Consistent trend was also found in the SRW collected from the same region. METH concentrations in the SRW were significantly and positively correlated with those in the RDW (p < 0.05), indicating that the discharge of RDW could be the important source of METH in the nearby rivers. The mean mass load of METH in the study rural area was about 65.8 mg·day-1·1000 inhabitants-1. Source apportionment showed that the abuse consumption was the main source of METH at most of sampling towns in the investigated rural area, and the mean mass load of METH at these towns (24.5 mg·day-1·1000 inhabitants-1) might reflect the abuse level of METH in this region. The disposal and illegal synthesis of METH could be important point sources, which led to the elevated METH level in the RDW. Risk assessment demonstrated that ALSs posed a minimal or medium risk to aquatic organisms. Our results provided valuable insights into the mass loads, source characteristics and ecological risks of ALSs in the rural area.


Assuntos
Anfetamina , Poluentes Químicos da Água , China , Monitoramento Ambiental , Rios , Poluentes Químicos da Água/análise
11.
Subst Use Misuse ; 56(12): 1831-1836, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34313194

RESUMO

Intercept surveys are a relatively inexpensive method to rapidly collect data on drug use. However, querying use of dozens of drugs can be time-consuming. We determined whether using a rapid screener is efficacious in detecting which participants use drugs and should be offered a full survey which asks more extensively about use.We surveyed 103 adults (age 18-29) on streets of Manhattan, NY in 2019 to test the reliability of a screener which queried past-year use of six drugs. Those reporting any drug use on the screener (and a third of those not reporting drug use) were offered the full survey which queried use of 97 drugs. We compared self-reported use on the screener to the full survey.Self-reported use of ecstasy, cocaine, and LSD had high test-retest reliability (Kappa = 0.90-1.00), and the screener had high sensitivity (1.00) and specificity (0.97-1.00) in detecting use of these drugs. Reliability for marijuana (Kappa = 0.62) and nonmedical opioid use (Kappa = 0.75) was lower. The screener had higher sensitivity (0.94) and lower specificity (0.64) in detecting marijuana use, and lower sensitivity (0.71) and higher specificity (0.98) in detecting nonmedical opioid use. Within the full survey, all participants reporting use of amphetamine (nonmedical use), shrooms, poppers, synthetic cannabinoids, synthetic cathinones, novel psychedelics, ketamine, or GHB reported use of at least one drug queried on the screener.Self-reported use of common drugs on a screener can reliably be used as an inclusion criterion for more extensive intercept surveys about drug use behavior.


Assuntos
Transtornos Relacionados ao Uso de Opioides , Preparações Farmacêuticas , Adolescente , Adulto , Anfetamina , Humanos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto Jovem
12.
Eur J Neurosci ; 54(3): 4934-4952, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34216157

RESUMO

Activation of cannabinoid 1 receptors (CB1 R) modulates multiple behaviours, including exploration, motor coordination and response to psychostimulants. It is known that CB1 R expressed by either excitatory or inhibitory neurons mediates different behavioural responses to CB1 R activation, yet the involvement of CB1 R expressed by medium spiny neurons (MSNs), the neuronal subpopulation that expresses the highest level of CB1 R in the CNS, remains unknown. We report a new genetically modified mouse line that expresses functional CB1 R in MSN on a CB1 R knockout (KO) background (CB1 R(MSN) mice). The absence of cannabimimetic responses measured in CB1 R KO mice was not rescued in CB1 R(MSN) mice, nor was decreased spontaneous locomotion, impaired instrumental behaviour or reduced amphetamine-triggered hyperlocomotion measured in CB1 R KO mice. Significantly, reduced novel environment exploration of an open field and absence of amphetamine sensitization (AS) measured in CB1 R KO mice were fully rescued in CB1 R(MSN) mice. Impaired motor coordination in CB1 R KO mice measured on the Rotarod was partially rescued in CB1 R(MSN) mice. Thus, CB1 R expressed by MSN control exploration, motor coordination, and AS. Our study demonstrates a new functional roles for cell specific CB1 R expression and their causal link in the control of specific behaviors.


Assuntos
Anfetamina , Canabinoides , Corpo Estriado , Receptor CB1 de Canabinoide , Anfetamina/farmacologia , Animais , Camundongos , Camundongos Knockout , Neurônios , Receptor CB1 de Canabinoide/genética
13.
Psychopharmacology (Berl) ; 238(9): 2601-2615, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34104987

RESUMO

BACKGROUND: Work in humans has shown that impulsivity can be advantageous in certain settings. However, evidence for so-called functional impulsivity is lacking in experimental animals. AIMS: This study investigated the contexts in which high impulsive (HI) rats show an advantage in performance compared with mid- (MI) and low impulsive (LI) rats. We also assessed the effects of dopaminergic and noradrenergic agents to investigate underlying neurotransmitter mechanisms. METHODS: We tested rats on a variable inter-trial interval (ITI) version of the 5-choice serial reaction time task (5CSRTT). Rats received systemic injections of methylphenidate (MPH, 1 mg/kg and 3 mg/kg), atomoxetine (ATO, 0.3 mg/kg and 1 mg/kg), amphetamine (AMPH, 0.2 mg/kg), the alpha-2a adrenoceptor antagonist atipamezole (ATI, 0.3 mg/kg) and the alpha-1 adrenoceptor agonist phenylephrine (PHEN, 1 mg/kg) prior to behavioural testing. RESULTS: Unlike LI rats, HI rats exhibited superior performance, earning more reinforcers, on short ITI trials, when the task required rapid responding. MPH, AMPH and ATI improved performance on short ITI trials and increased impulsivity in long ITI trials, recapitulating the behavioural profile of HI. In contrast, ATO and PHEN impaired performance on short ITI trials and decreased impulsivity, thus mimicking the behavioural profile of LI rats. The effects of ATO were greater on MI rats and LI rats. CONCLUSIONS: These findings indicate that impulsivity can be advantageous when rapid focusing and actions are required, an effect that may depend on increased dopamine neurotransmission. Conversely, activation of the noradrenergic system, with ATO and PHEN, led to a general inhibition of responding.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Anfetamina/farmacologia , Animais , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Comportamento de Escolha , Comportamento Impulsivo , Ratos , Tempo de Reação
14.
J Neurochem ; 158(4): 833-836, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34184261

RESUMO

Dopamine dyshomeostasis is a driving factor of nigrostriatal degeneration in Parkinson's disease (PD). Accumulation of cytosolic dopamine at striatal projections results in the buildup of autoxidation products, which generates protein adducts and exacerbate oxidative stress. Moreover, an excessive rate of dopamine degradation results in accumulation of 3,4-dihydroxyphenylacetaldehyde (DOPAL), a toxic metabolite which rapidly reacts with other proteins. These events lead to protein misfolding and cross-linking as well as mitochondrial and lysosomal dysfunction, the main pathological mechanisms underscoring dopaminergic neuron loss in PD. In this issue of Journal of Neurochemistry, Vecchio et al. generated and characterized a new in vivo model of chronic dopamine accumulation through the overexpression of a hyperactive form of tyrosine hydroxylase (TH-HI), the rate-limiting step enzyme in dopamine biosynthesis. At 3-5 months of age, TH-HI mice displayed increased striatal dopamine content, exacerbated dopamine catabolism, and augmented responses to amphetamine. This correlated with enhanced oxidative stress and DOPAL buildup, highlighting a catechol-induced neurotoxic vicious cycle that may anticipate a parkinsonian-like phenotype in aged mice. This novel TH-HI animal model represents an exciting new tool to unravel the molecular mechanisms underlying dopamine disequilibrium, catecholamine autotoxicity, and neurodegeneration in PD.


Assuntos
Neurônios Dopaminérgicos , Doença de Parkinson , Anfetamina , Animais , Catecolaminas , Dopamina , Camundongos , Estresse Oxidativo , Tirosina 3-Mono-Oxigenase
15.
Am J Psychiatry ; 178(8): 744-751, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34086483

RESUMO

OBJECTIVE: Psychostimulants are first-line pharmacological treatments for attention deficit hyperactivity disorder (ADHD), although symptom reduction varies widely between patients and these individual differences in treatment response are poorly understood. The authors sought to examine whether the resting-state functional connectivity within and between cingulo-opercular, striato-thalamic, and default mode networks was associated with treatment response to psychostimulant medication, and whether this relationship changed with development. METHODS: Patients with ADHD (N=110; 196 observations; mean age at first observation, 10.83 years, SD=2.2) and typically developing control subjects (N=142; 330 observations; mean age at first observation, 10.49 years, SD=2.81) underwent functional neuroimaging on up to five occasions during development (age range, 6-17 years). For patients, symptoms were assessed on and off psychostimulant medication (methylphenidate-based treatments: N=132 observations, 67%; amphetamine-based treatments: N=64 observations, 33%) using the Diagnostic Interview for Children and Adolescents for parents. Linear mixed-effects models examined whether resting-state connectivity was associated with treatment response and its interaction with age. Comparisons with typically developing control subjects were performed to contextualize any significant associations. RESULTS: Resting-state connectivity within the cingulo-opercular network was associated with a significant interaction between treatment response and age. Specifically, worse responses to treatment compared with better responses to treatment among patients and compared with typically developing control subjects were associated with an atypical increase in cingulo-opercular connectivity with increasing age from childhood to adolescence. CONCLUSIONS: This work delineates how resting-state connectivity may be associated over development with response to psychostimulants in ADHD. Functioning and development within the cingulo-opercular network may warrant further investigation as a contributor to differential response to psychostimulants.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Adolescente , Anfetamina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Criança , Feminino , Neuroimagem Funcional , Humanos , Entrevista Psicológica , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Metilfenidato/uso terapêutico , Vias Neurais , Resultado do Tratamento
16.
Exp Neurol ; 342: 113754, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34000249

RESUMO

The alkaloid ephedrine derived from Ephedra vulgaris is at the origin of psychostimulant-drugs as amphetamine. These drugs have been principally utilized for medical treatments in the past, while their utilization has been largely reduced from the 1970s when the high risk of addiction and abuse has been recognized. The first reported treatments were as anti-asthmatics and to contrast narcolepsy until their recreational stimulant and anorexic effects were reported. Benzedrine and Pervitin use were of great importance during the Second World War due to their abundant utilization among military troops. Nowadays the use of selective amphetamine-like drugs is limited to ADHD treatment.


Assuntos
Doença da Altitude/história , Anfetamina/história , Transtorno do Deficit de Atenção com Hiperatividade/história , Estimulantes do Sistema Nervoso Central/história , Fadiga/história , Doença da Altitude/tratamento farmacológico , Anfetamina/administração & dosagem , Animais , Conflitos Armados/história , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/administração & dosagem , Fadiga/tratamento farmacológico , História do Século XIX , História do Século XX , História do Século XXI , Humanos
17.
Eur J Pharmacol ; 904: 174148, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-33961872

RESUMO

As drug addiction may result from pathological usurpations of learning and memory's neural mechanisms, we focused on the amphetamine-induced time-dependent neurochemical changes associated with neural plasticity. We used juvenile rats as the risk for drug abuse is higher during adolescence. Experiment 1 served to define the appropriate amphetamine dose and the neurochemical effects of a single administration. In experiment 2, rats received seven amphetamine or saline injections in the open-field test throughout a twelve-day period. We measured the mRNA levels of 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 monoamines and amino-acids contents in the nucleus accumbens and the dorsal striatum 45, 90, and 180 min after the last injection. We found that amphetamine changed gene expression only at certain time points and in a dose and region-dependent manner. Repeated but not single administrations upregulated accumbal and striatal BDNF (180 min) and striatal pri-miR-132 (90 min) expression, while downregulated accumbal CREB levels (90 min). As only some drug users develop addiction, we compared brain parameters between low and high amphetamine responders. Prone subjects characterized by having reduced striatal 5-HT metabolism, higher accumbal BDNF and TrkB expression, and lower levels of CREB in the dorsal striatum and p250GAP in both regions. Thus, individual differences in drug-induced changes in neurotransmission and gene expression in nigrostriatal and mesolimbic dopaminergic pathways may underlie the plasticity adaptations associated with behavioral sensitization to amphetamine.


Assuntos
Anfetamina/farmacologia , Monoaminas Biogênicas/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , Corpo Estriado/metabolismo , Anfetamina/administração & dosagem , Animais , Antecipação Psicológica/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Corpo Estriado/efeitos dos fármacos , Correlação de Dados , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Hipercinese/induzido quimicamente , Injeções Intraperitoneais , Masculino , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Ratos Wistar , Fatores de Tempo
18.
J Neurochem ; 158(4): 960-979, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33991113

RESUMO

In Parkinson's disease, dopamine-containing nigrostriatal neurons undergo profound degeneration. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine biosynthesis. TH increases in vitro formation of reactive oxygen species, and previous animal studies have reported links between cytosolic dopamine build-up and oxidative stress. To examine effects of increased TH activity in catecholaminergic neurons in vivo, we generated TH-over-expressing mice (TH-HI) using a BAC-transgenic approach that results in over-expression of TH with endogenous patterns of expression. The transgenic mice were characterized by western blot, qPCR, and immunohistochemistry. Tissue contents of dopamine, its metabolites, and markers of oxidative stress were evaluated. TH-HI mice had a 3-fold increase in total and phosphorylated TH levels and an increased rate of dopamine synthesis. Coincident with elevated dopamine turnover, TH-HI mice showed increased striatal production of H2 O2 and reduced glutathione levels. In addition, TH-HI mice had elevated striatal levels of the neurotoxic dopamine metabolites 3,4-dihydroxyphenylacetaldehyde and 5-S-cysteinyl-dopamine and were more susceptible than wild-type mice to the effects of amphetamine and methamphetamine. These results demonstrate that increased TH alone is sufficient to produce oxidative stress in vivo, build up autotoxic dopamine metabolites, and augment toxicity.


Assuntos
Anfetamina/farmacologia , Catecolaminas/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , Estresse Oxidativo , Tirosina 3-Mono-Oxigenase/metabolismo , Ácido 3,4-Di-Hidroxifenilacético/análogos & derivados , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Dopamina/análogos & derivados , Dopamina/metabolismo , Feminino , Dosagem de Genes , Glutationa/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Neurônios/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/genética
19.
Health Sociol Rev ; 30(2): 111-126, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34018913

RESUMO

Amphetamine Type Stimulants (ATS) are increasingly used drugs globally. There is limited evidence about what shapes ATS use at critical turning points located within drug using pathways. Using turning point theory, as part of a life course approach, the ATTUNE study aimed to understand which social, economic and individual factors shape pathways into and out of ATS use. Qualitative, semi-structured interviews (n = 70) were undertaken with individuals who had used ATS, or had been exposed to them at least once. Our findings show that turning points for initiation were linked to pleasure, curiosity, boredom and declining mental health; increased use was linked to positive effects experienced at initiation and multiple life-stressors, leading to more intense use. Decreased use was prompted by pivotal events and sustained through continued wellbeing, day-to-day structure, and non-using social networks. We argue that the heterogeneity of these individuals challenges stereotypes of stimulant use allied to nightclubs and 'hedonism'. Further, at critical turning points for recovery, the use of services for problematic ATS consumption was low because users prioritised their alcohol or opioid use when seeking help. There is a need to develop service provision, training, and better outreach to individuals who need support at critical turning points.


Assuntos
Estimulantes do Sistema Nervoso Central , Transtornos Relacionados ao Uso de Substâncias , Anfetamina , Estimulantes do Sistema Nervoso Central/efeitos adversos , Cognição , Humanos , Pesquisa Qualitativa
20.
Analyst ; 146(10): 3336-3345, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-33999061

RESUMO

The abuse of methamphetamine (MA) is to date detected and subsequently verified through the monitoring of MA and its metabolites within biological specimens. Current approaches require complex sample purification strategies alongside significant analysis time. Given the high prevalence of MA within the global drug market, there remains a need for rapid, portable and alternative screening approaches appropriate for direct detection within biological matrices for employment across the forensic and clinical environments. This contribution illustrates the use of an electrochemiluminescence (ECL) strategy for the screening of MA, amphetamine (AMP) and para hydroxy-methamphetamine (pOH-MA) for such applications. The sensing system showed ideal analytical performance with linear ranges at forensically relevant concentrations of 0.1 µM to 0.5 mM for MA, 10 µM to 1 mM AMP and 10 µM to 5 mM for pOH-MA, and superb detection limits of 74.6 nM, 6 µM and 82. µM for MA, AMP and pOH-MA respectively. Furthermore, the sensor was successful in the detection of MA, AMP and pOH-AMP within human pooled serum, artificial urine and saliva, without any prior purification strategies. Here a portable ECL sensor is detailed for the successful employment of the direct screening of these amphetamine type substances and their corresponding metabolites at clinically and forensically relevant concentrations within a range of biological matrices. This approach successfully represents a strong proof-of-concept, for a novel, simple and rapid screening method with significant potential for high-throughput screening of biological samples for drug metabolites, widening the avenues where ECL sensors could be employed.


Assuntos
Metanfetamina , Anfetamina , Humanos , Medições Luminescentes , Saliva , Detecção do Abuso de Substâncias
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