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1.
Adv Pharmacol ; 99: 145-168, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38467480

RESUMO

Methamphetamine (METH) is the most commonly misused amphetamine-type stimulant throughout the globe. METH is very rewarding, and its misuse can lead to a diagnosis of METH use disorder (MUD). Although METH use is observed in both sexes, there are, however, reported differences in the clinical manifestations of METH use and its consequences. These observations indicate the need for more research on the long-term sex-dependent consequences of METH taking in both preclinical and clinical settings. In effect, sex is a biological variable that can impact conclusions drawn from various basic and clinical studies. Thus, the present chapter provides a succinct review of the current state of the research on METH and its sex-associated consequences. In addition to behavioral and cognitive aspects of METH use, we discuss METH-induced changes in neurotransmitter systems and structures in the brain. Thus, the book chapter serves to highlight the significance of sex as a critical element that needs to be considered during discussions of novel therapeutic approaches to MUD.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Estimulantes do Sistema Nervoso Central , Metanfetamina , Animais , Feminino , Humanos , Masculino , Metanfetamina/efeitos adversos , Caracteres Sexuais , Encéfalo , Mamíferos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Transtornos Relacionados ao Uso de Anfetaminas/genética , Transtornos Relacionados ao Uso de Anfetaminas/psicologia
2.
Adv Pharmacol ; 99: 125-144, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38467479

RESUMO

Use of amphetamines during adolescence, a critical period of brain development and reorganization, may lead to particularly adverse outcomes that are long-lasting. Similarly, female users may be uniquely vulnerable to certain aspects of drug use. A recognition of the role of use during adolescence and sex on outcomes of amphetamine and methamphetamine exposure are of critical importance in understanding and treating substance use disorders. This chapter highlights what human research, which has been largely epidemiological, suggests about sex and age differences in drug use patterns and outcomes. We also discuss work in laboratory animals that has typically utilized rats or mice exposed to drugs in a non-contingent manner (i.e., involuntarily) or through volitional self-administration. Lastly, we draw attention to the fact that advancing our understanding of the effects of amphetamine and methamphetamine use, the development of problematic drug taking, and the mechanisms that contribute to relapse will require an emphasis on inclusion of age and sex as moderating factors in future studies.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Metanfetamina , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Feminino , Humanos , Ratos , Camundongos , Animais , Anfetaminas/efeitos adversos , Metanfetamina/efeitos adversos , Anfetamina
3.
Addict Biol ; 29(3): e13383, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38488760

RESUMO

Repeated abuse of methamphetamine (METH) can cause dependence, repeated relapse of psychotic symptoms, compulsive drug-seeking behaviour, and various neurological symptoms. These long-term biological changes may be associated with epigenetic mechanisms; however, the association between METH use and epigenetic mechanisms has been poorly investigated. Thus, we performed an epigenome-wide association study of METH dependence using genomic DNA extracted from the blood samples of 24 patients with METH dependence and 24 normal controls. All participants were of Japanese descent. We tested the association between METH dependence and DNA methylation using linear regression analysis. We found epigenome-wide significant associations at four CpG sites, one of which occurred in the CNOT1 gene and another in the PUM1 gene. We especially noted the CNOT1 and PUM1 genes as well as several other genes that indicated some degree of association with METH dependence. Among the relatively enriched Gene Ontology terms, we were interested in terms of mRNA metabolism, respirasome, and excitatory extracellular ligand-gated ion channel activity. Among the relatively enriched Kyoto Encyclopedia of Genes and Genome pathways, we noted pathways of several neurological diseases. Our results indicate that genetic changes akin to those in other psychiatric or neurodegenerative disorders may also occur via epigenetic mechanisms in patients with METH dependence.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Metanfetamina , Humanos , Epigenoma/genética , Transtornos Relacionados ao Uso de Anfetaminas/genética , Epigênese Genética/genética , Metilação de DNA , Estudo de Associação Genômica Ampla , Proteínas de Ligação a RNA/genética , Fatores de Transcrição/genética
4.
CNS Neurosci Ther ; 30(2): e14580, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38421126

RESUMO

INTRODUCTION: Methamphetamine (MA) abuse is a major public problem, and impulsivity is both a prominent risk factor and a consequence of addiction. Hence, clarifying the biological mechanism of impulsivity may facilitate the understanding of addiction to MA. The microbiota-gut-brain axis was suggested to underlie a biological mechanism of impulsivity induced by MA. METHODS: We therefore recruited 62 MA addicts and 50 healthy controls (HCs) to investigate the alterations in impulsivity and fecal microbiota and the associations between them in the MA group. Thereafter, 25 MA abusers who abstained from MA for less than 3 months were followed up for 2 months to investigate the relationship between impulsivity and microbiota as abstinence became longer. 16S rRNA sequencing was conducted for microbiota identification. RESULTS: Elevated impulsivity and dysbiosis characterized by an increase in opportunistic pathogens and a decrease in probiotics were identified in MA abusers, and both the increased impulsivity and disrupted microbiota tended to recover after longer abstinence from MA. Impulsivity was related to microbiota, and the effect of MA abuse on impulsivity was mediated by microbiota. CONCLUSION: Our findings potentially highlighted the importance of abstention and implicated the significant role of the microbiota-gut-brain axis in the interrelationship between microbiota and behaviors, as well as the potential of microbiota as a target for intervention of impulsivity.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Metanfetamina , Microbiota , Humanos , Metanfetamina/efeitos adversos , RNA Ribossômico 16S/genética , Comportamento Impulsivo
6.
Cereb Cortex ; 34(2)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38300175

RESUMO

Methamphetamine is a highly addictive psychostimulant drug that is abused globally and is a serious threat to health worldwide. Unfortunately, the specific mechanism underlying addiction remains unclear. Thus, this study aimed to investigate the characteristics of functional connectivity in the brain network and the factors influencing methamphetamine use disorder in patients using magnetic resonance imaging. We included 96 abstinent male participants with methamphetamine use disorder and 46 age- and sex-matched healthy controls for magnetic resonance imaging. Compared with healthy controls, participants with methamphetamine use disorder had greater impulsivity, fewer small-world attributes of the resting-state network, more nodal topological attributes in the cerebellum, greater functional connectivity strength within the cerebellum and between the cerebellum and brain, and decreased frontoparietal functional connectivity strength. In addition, after controlling for covariates, the partial correlation analysis showed that small-world properties were significantly associated with methamphetamine use frequency, psychological craving, and impulsivity. Furthermore, we revealed that the small-word attribute significantly mediated the effect of methamphetamine use frequency on motor impulsivity in the methamphetamine use disorder group. These findings may further improve our understanding of the neural mechanism of impulse control dysfunction underlying methamphetamine addiction and assist in exploring the neuropathological mechanism underlying methamphetamine use disorder-related dysfunction and rehabilitation.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Estimulantes do Sistema Nervoso Central , Metanfetamina , Humanos , Masculino , Metanfetamina/efeitos adversos , Encéfalo/diagnóstico por imagem , Transtornos Relacionados ao Uso de Anfetaminas/diagnóstico por imagem , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Mapeamento Encefálico , Imageamento por Ressonância Magnética
7.
J Addict Med ; 18(2): 180-184, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38227855

RESUMO

OBJECTIVE: Increasing rates of methamphetamine (METH) use, use disorders, and related overdoses are a growing public health problem. There are a lack of protocols addressing METH intoxication and withdrawal symptoms that manifest during acute withdrawal treatment resulting in inpatient management difficulties and premature discharges. This report presents a novel treatment protocol comprised of behavior-targeted and pharmacological components that aims to reduce the intensity and duration of METH intoxication and withdrawal related symptoms during early treatment, improve retention, and provide clinicians with a tool to meet this growing problem. METHODS: The protocol was developed by a team of addiction physicians and other clinical staff. Clinical and administrative staff at a community acute stabilization unit were trained and the protocol was implemented with patients presenting with METH use. Pharmacological interventions, including ascorbic acid, antipsychotics, and other sedatives are discussed, as are behavior-based orders. A retrospective quality assurance examination was conducted on patient characteristics and outcomes as well as focus groups with nursing staff. RESULTS: A total of 23 patients consecutively admitted to the unit used the protocol (100% male). Most patients (67%) displayed symptoms of METH use or withdrawal. Behavior-related interventions were used in 52% of patients, while 48% received behavior-related and pharmacological measures. Patient completion of the protocol was 83%, and the protocol's utility was supported by nursing staff. CONCLUSIONS: This retrospective evaluation of a novel METH withdrawal treatment protocol suggests feasibility, tolerability, and preliminary evidence of effectiveness, providing clinicians with a new tool that requires further study.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Estimulantes do Sistema Nervoso Central , Metanfetamina , Transtornos Relacionados ao Uso de Opioides , Síndrome de Abstinência a Substâncias , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pacientes Internados , Metanfetamina/efeitos adversos
8.
Addict Biol ; 29(1): e13356, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38221809

RESUMO

People with methamphetamine use disorder (MUD) struggle to shift their behaviour from methamphetamine-orientated habits to goal-oriented choices. The model-based/model-free framework is well suited to understand this difficulty by unpacking the computational mechanisms that support experienced-based (model-free) and goal-directed (model-based) choices. We aimed to examine whether 1) participants with MUD differed from controls on behavioural proxies and/or computational mechanisms of model-based/model-free choices; 2) model-based/model-free decision-making correlated with MUD symptoms; and 3) model-based/model-free deficits improved over six weeks in the group with MUD. Participants with MUD and controls with similar age, IQ and socioeconomic status completed the Two-Step Task at treatment commencement (MUD n = 30, Controls n = 31) and six weeks later (MUD n = 23, Controls n = 26). We examined behavioural proxies of model-based/model-free decisions using mixed logistic regression, and their underlying mechanisms using computational modelling. At a behavioural level, participants with MUD were more likely to switch their choices following rewarded actions, although this pattern improved at follow up. At a computational level, groups were similar in their use of model-based mechanisms, but participants with MUD were less likely to apply model-free mechanisms and less likely to repeat rewarded actions. We did not find evidence that individual differences in model-based or model-free parameters were associated with greater severity of methamphetamine dependence, nor did we find that group differences in computational parameters changed between baseline and follow-up assessment. Decision-making challenges in people with MUD are likely related to difficulties in pursuing choices previously associated with positive outcomes.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Metanfetamina , Humanos , Recém-Nascido , Recompensa , Motivação
9.
Int J Mol Sci ; 25(2)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38256016

RESUMO

Methamphetamine (METH) abuse inflicts both physical and psychological harm. While our previous research has established the regulatory role of miR-29c-3p in behavior sensitization, the underlying mechanisms and target genes remain incompletely understood. In this study, we employed the isobaric tags for relative and absolute quantitation (iTRAQ) technique in conjunction with Ingenuity pathway analysis (IPA) to probe the putative molecular mechanisms of METH sensitization through miR-29c-3p inhibition. Through a microinjection of AAV-anti-miR-29c-3p into the nucleus accumbens (NAc) of mice, we observed the attenuation of METH-induced locomotor effects. Subsequent iTRAQ analysis identified 70 differentially expressed proteins (DEPs), with 22 up-regulated potential target proteins identified through miR-29c-3p target gene prediction and IPA analysis. Our focus extended to the number of neuronal branches, the excitatory synapse count, and locomotion-related pathways. Notably, GPR37, NPC1, and IREB2 emerged as potential target molecules for miR-29c-3p regulation, suggesting their involvement in the modulation of METH sensitization. Quantitative PCR confirmed the METH-induced aberrant expression of Gpr37, Npc1, and Ireb2 in the NAc of mice. Specifically, the over-expression of miR-29c-3p led to a significant reduction in the mRNA level of Gpr37, while the inhibition of miR-29c-3p resulted in a significant increase in the mRNA level of Gpr37, consistent with the regulatory principle of miRNAs modulating target gene expression. This suggests that miR-29c-3p potentially influences METH sensitization through its regulation of neuroplasticity. Our research indicates that miR-29c-3p plays a crucial role in regulating METH-induced sensitization, and it identified the potential molecular of miR-29c-3p in regulating METH-induced sensitization.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Metanfetamina , MicroRNAs , Doença de Niemann-Pick Tipo C , Animais , Camundongos , Núcleo Accumbens , Metanfetamina/farmacologia , MicroRNAs/genética , Plasticidade Neuronal/genética , RNA Mensageiro , Receptores Acoplados a Proteínas G
10.
Child Abuse Negl ; 147: 106579, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38048654

RESUMO

BACKGROUND: Childhood trauma is associated with substance use disorders, including methamphetamine use disorder (MUD). Oxytocin, involved in social bonding, stress regulation, and reward processing, may influence addiction vulnerability and impulsivity in individuals with a history of childhood trauma. OBJECTIVE: To investigate the relationships among childhood trauma, oxytocin levels, impulsivity, and the age of first methamphetamine use in individuals with MUD. PARTICIPANTS AND SETTING: The study included 298 male participants (148 individuals with MUD and 150 healthy controls) from both probation offices and psychiatric clinics. METHODS: Childhood trauma was assessed using the Childhood Trauma Questionnaire-Short Form (CTQ-SF), impulsivity with the Barratt Impulsiveness Scale-11 (BIS-11), and plasma oxytocin levels were obtained. RESULTS: Individuals with MUD exhibited higher levels of childhood trauma, impulsivity, and lower plasma oxytocin levels compared to healthy controls. Childhood trauma was associated with a younger age of first methamphetamine use, higher impulsivity, and lower oxytocin levels among individuals with MUD. Plasma oxytocin levels partially mediated the relationship between childhood trauma and both the age of first methamphetamine use and impulsivity. Serial mediation analysis demonstrated that oxytocin levels and impulsivity sequentially mediated the relationship between childhood trauma and the age of first methamphetamine use. CONCLUSIONS: The findings reveal the complex interplay among childhood trauma, oxytocin, impulsivity, and methamphetamine use, emphasizing the importance of considering these factors in prevention and intervention strategies for MUD. Future research should explore oxytocin and impulsivity-focused interventions to mitigate the effects of childhood trauma and reduce MUD development risk.


Assuntos
Experiências Adversas da Infância , Transtornos Relacionados ao Uso de Anfetaminas , Metanfetamina , Testes Psicológicos , Autorrelato , Humanos , Masculino , Ocitocina , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Comportamento Impulsivo/fisiologia
12.
J Int Neuropsychol Soc ; 30(1): 84-93, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37553288

RESUMO

OBJECTIVE: Methamphetamine and cannabis are two widely used, and frequently co-used, substances with possibly opposing effects on the central nervous system. Evidence of neurocognitive deficits related to use is robust for methamphetamine and mixed for cannabis. Findings regarding their combined use are inconclusive. We aimed to compare neurocognitive performance in people with lifetime cannabis or methamphetamine use disorder diagnoses, or both, relative to people without substance use disorders. METHOD: 423 (71.9% male, aged 44.6 ± 14.2 years) participants, stratified by presence or absence of lifetime methamphetamine (M-/M+) and/or cannabis (C-/C+) DSM-IV abuse/dependence, completed a comprehensive neuropsychological, substance use, and psychiatric assessment. Neurocognitive domain T-scores and impairment rates were examined using multiple linear and binomial regression, respectively, controlling for covariates that may impact cognition. RESULTS: Globally, M+C+ performed worse than M-C- but better than M+C-. M+C+ outperformed M+C- on measures of verbal fluency, information processing speed, learning, memory, and working memory. M-C+ did not display lower performance than M-C- globally or on any domain measures, and M-C+ even performed better than M-C- on measures of learning, memory, and working memory. CONCLUSIONS: Our findings are consistent with prior work showing that methamphetamine use confers risk for worse neurocognitive outcomes, and that cannabis use does not appear to exacerbate and may even reduce this risk. People with a history of cannabis use disorders performed similarly to our nonsubstance using comparison group and outperformed them in some domains. These findings warrant further investigation as to whether cannabis use may ameliorate methamphetamine neurotoxicity.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Cannabis , Transtornos Cognitivos , Metanfetamina , Humanos , Masculino , Feminino , Metanfetamina/efeitos adversos , Cannabis/efeitos adversos , Transtornos Cognitivos/etiologia , Transtornos Relacionados ao Uso de Anfetaminas/complicações , Testes Neuropsicológicos
13.
mSystems ; 9(1): e0099123, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38112416

RESUMO

Drug addiction can seriously damage human physical and mental health, while detoxification is a long and difficult process. Although studies have reported changes in the oral microbiome of methamphetamine (METH) users, the role that the microbiome plays in the process of drug addiction is still unknown. This study aims to explore the function of the microbiome based on analysis of the variations in the oral microbiome and metabolome of METH users. We performed the 16S rRNA sequencing analysis based on the oral saliva samples collected from 278 METH users and 105 healthy controls (CTL). In addition, the untargeted metabolomic profiling was conducted based on 220 samples. Compared to the CTL group, alpha diversity was reduced in the group of METH users and the relative abundances of Peptostreptococcus and Gemella were significantly increased, while the relative abundances of Campylobacter and Aggregatibacter were significantly decreased. Variations were also detected in oral metabolic pathways, including enhanced tryptophan metabolism, lysine biosynthesis, purine metabolism, and steroid biosynthesis. Conversely, the metabolic pathways of porphyrin metabolism, glutathione metabolism, and pentose phosphate were significantly reduced. It was speculated that four key microbial taxa, i.e., Peptostreptococcus, Gemella, Campylobacter, and Aggregatibacter, could be involved in the toxicity and addiction mechanisms of METH by affecting the above metabolic pathways. It was found that with the increase of drug use years, the content of tryptamine associated with neuropsychiatric disorders was gradually increased. Our study provides novel insights into exploring the toxic damage and addiction mechanisms underlying the METH addiction.IMPORTANCEIt was found that with the increase of drug use years, the content of tryptamine associated with neuropsychiatric disorders gradually increased. The prediction models based on oral microbiome and metabolome could effectively predict the methamphetamine (METH) smoking. Our study provides novel insights into the exploration of the molecular mechanisms regulating the toxic damage and addiction of METH as well as new ideas for early prevention and treatment strategies of METH addiction.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Metanfetamina , Microbiota , Humanos , Metanfetamina/efeitos adversos , RNA Ribossômico 16S/genética , Transtornos Relacionados ao Uso de Anfetaminas/complicações , Metaboloma , Microbiota/genética , Triptaminas
14.
Rev Neurol ; 77(12): 293-298, 2023 Dec 16.
Artigo em Espanhol | MEDLINE | ID: mdl-38095053

RESUMO

INTRODUCTION: Chronic non-recreational use of methamphetamine (shabu) is increasing among the Filipino population in Barcelona. The Asian population presents a different stroke pattern, with a higher incidence of haemorrhage, and different vascular risk factors and health behaviours. The objective of this study is to describe the stroke profile and incidence of methamphetamine use in patients of Filipino origin admitted to our centre. PATIENTS AND METHODS: Demographic data, vascular risk factors, clinical data and prognosis were recorded. Methamphetamine exposure was analysed in plasma samples collected on admission, which were then analysed by liquid chromatography-mass spectrometry. RESULTS: Of a total of 6,418 stroke patients, 73 (1.1%) were identified as being of Filipino origin. The mean age was 54.4 ± 12.1 years, 54% were male and the stroke was ischaemic in 64.4% of cases. Arterial hypertension was the main risk factor. Ten (13.7%) patients tested positive for methamphetamine and amphetamine. These results confirm recent substance use prior to the stroke, mostly in men (80%). In patients who were consumers, 60% had a haemorrhagic stroke, with a poor functional prognosis at three months in 55.6% of patients. CONCLUSIONS: In our setting, patients of Filipino ethnicity admitted for stroke related to the consumption of shabu belonged a younger age bracket, with a lower prevalence of vascular risk factors and a predominance of the haemorrhagic subtype. Methamphetamine testing in Filipino stroke patients is recommended due to the high prevalence of methamphetamine use in our country.


TITLE: Perfil clínico y abuso de metanfetamina no recreativa (shabú) entre los pacientes con ictus en la población filipina.Introducción. En la población filipina de Barcelona está aumentando el consumo crónico no recreativo de metanfetaminas (shabú). La población asiática presenta un patrón de ictus diferente, con mayor incidencia de hemorragias, y diferentes factores de riesgo vascular y conductas de salud. El objetivo es describir el perfil de ictus e incidencia de consumo de metanfetaminas en pacientes de origen filipino ingresados en nuestro centro. Pacientes y métodos. Se registraron datos demográficos, factores de riesgo vascular, datos clínicos y pronóstico. Se analizó la exposición a metanfetamina en muestras de plasma recogidas en el ingreso, que se analizaron por cromatografía líquida-espectrometría de masas. Resultados. Del total de 6.418 pacientes con ictus, se identificó a 73 pacientes filipinos (1,1%). La edad media era de 54,4 ± 12,1 años, el 54% eran hombres y el ictus era isquémico en el 64,4%. La hipertensión arterial fue el principal factor de riesgo. Diez (13,7%) pacientes dieron positivo a metanfetamina y anfetamina. Estos resultados confirman un consumo reciente de sustancias previo al ictus, principalmente en hombres (80%). En pacientes consumidores, un 60% presentaba un ictus hemorrágico, con mal pronóstico funcional a tres meses en el 55,6% de los pacientes. Conclusiones. En nuestro medio, los pacientes de etnia filipina ingresados por ictus en relación con consumo de shabú presentaron un perfil de edad más joven, con menor prevalencia de factores de riesgo vascular y predominio del subtipo hemorrágico. Se recomienda la determinación de metanfetamina en los pacientes filipinos con ictus debido a la alta prevalencia del consumo de metanfetamina en nuestro país.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Metanfetamina , Acidente Vascular Cerebral , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Filipinas/epidemiologia , Metanfetamina/efeitos adversos , Metanfetamina/análise , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Transtornos Relacionados ao Uso de Anfetaminas/complicações , Transtornos Relacionados ao Uso de Anfetaminas/epidemiologia , Anfetamina
15.
BMC Psychiatry ; 23(1): 852, 2023 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978352

RESUMO

Methamphetamine (MA) abuse is recognized as a brain disorder, and physical activity has clear benefits for MA use disorders. The specific mechanisms by which physical activity alleviates MA use disorders are currently not fully understood. Based on this, the present study used untargeted metabolomics using liquid chromatography-mass spectrometry (LC-MS) to analyze the metabolic changes induced by MA in the brains of mice by exercise intervention. It was found that after 2 weeks of treadmill training, aerobic exercise modulated MA-induced brain metabolic disorders, in which 129 metabolites existed that were significantly differentiated in response to MA induction, and 32 metabolites were significantly affected by exercise. These differential metabolites were mainly enriched in glycerophospholipid metabolism, steroid hormone biosynthesis and degradation, and renin-angiotensin system pathways. To our knowledge, this study is the first to use LC-MS to investigate the effects of aerobic exercise on MA-induced brain metabolic profiling. The findings of this study provide new insights into exercise therapy using MA.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Metanfetamina , Camundongos , Animais , Metanfetamina/efeitos adversos , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem , Encéfalo/metabolismo
17.
Neurotox Res ; 41(6): 741-751, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37904065

RESUMO

Addiction is a serious public health problem, and the current pharmacotherapy is unable to prevent drug use reinstatement. Studies have focused on physical exercise as a promising coadjuvant treatment. Our research group recently showed beneficial neuroadaptations in the dopaminergic system related to amphetamine-relapse prevention involving physical exercise-induced endogenous opioid system activation (EXE-OS activation). In this context, additional mechanisms were explored to understand the exercise benefits on drug addiction. Male rats previously exposed to amphetamine (AMPH, 4.0 mg/kg) for 8 days were submitted to physical exercise for 5 weeks. EXE-OS activation was blocked by naloxone administration (0.3 mg/kg) 5 min before each physical exercise session. After the exercise protocol, the rats were re-exposed to AMPH for 3 days, and in sequence, euthanasia was performed and the VTA and NAc were dissected. In the VTA, our findings showed increased immunocontent of proBDNF, BDNF, and GDNF and decreased levels of AMPH-induced TrkB; therefore, EXE-OS activation increased all these markers and naloxone administration prevented this exercise-induced effect. In the NAc, the same molecular markers were also increased by AMPH and decreased by EXE-OS activation. In this study, we propose a close relation between EXE-OS activation beneficial influence and a consequent neuroadaptation on neurotrophins and dopaminergic system levels in the mesolimbic brain area, preventing the observed AMPH-relapse behavior. Our outcomes bring additional knowledge concerning addiction neurobiology understanding and show that EXE-OS activation may be a potential adjuvant tool in drug addiction therapy.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Analgésicos Opioides , Ratos , Masculino , Animais , Fatores de Crescimento Neural/farmacologia , Anfetamina , Encéfalo , Naloxona/farmacologia , Núcleo Accumbens
18.
Behav Brain Res ; 455: 114673, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37717660

RESUMO

Methamphetamine (METH) is a psychostimulant drug that has become increasingly popular in recent years, with overdose deaths more than doubling during the second half of the 2010s. As methamphetamine use disorder rates continue to increase, finding effective treatment strategies to decrease METH dependence is important. Animal studies are well-suited for studying the neurobiological mechanisms underlying addiction-like behaviors. Although individuals can ingest METH orally, few studies have examined oral METH self-administration in animals. Mice show decreased responding for oral METH as the response requirement increases across sessions. The purpose of the current study was to determine if rats show a similar decrease in motivation to earn oral METH across increasing response requirements. Sixteen Sprague Dawley rats were trained to emit a response in an aperture to receive a 0.1-ml METH solution (40 mg/l) according to an FR 1 schedule. The FR requirement increased across sessions to a terminal FR 10. Responses for METH decreased significantly when an FR 10 schedule was used. These results suggest that rats, similarly to mice, have low motivation to self-administer oral METH.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Estimulantes do Sistema Nervoso Central , Metanfetamina , Ratos , Camundongos , Animais , Metanfetamina/farmacologia , Ratos Sprague-Dawley , Motivação , Transtornos Relacionados ao Uso de Anfetaminas/tratamento farmacológico , Autoadministração/métodos
19.
Int J Drug Policy ; 121: 104189, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37708599

RESUMO

BACKGROUND: Regular methamphetamine use can cause a range of physical, psychological and social harms. Stigma is one factor that impacts engagement and successful completion of treatment. In Australia, Aboriginal and Torres Strait Islander people who regularly use methamphetamine experience multiple stigmas, which further compounds access to treatment and quality of life. This paper explores the cumulative and compounding effects of participating in a stigmatised activity such as illicit drug use in relation to the stigma experienced by Aboriginal and Torres Strait Islander people as a population marginalised through colonisation. METHODS: Ten sites nationally participated in a cross-sectional survey measuring a range of factors including psychosocial stress in methamphetamine users. The survey sample size was 734, with 59% identifying as Aboriginal and Torres Strait Islander (n = 433). In addition, a total of 147 mainly Aboriginal and Torres Strait Islander people who use methamphetamine, community and family members, and service providers took part in a total of 19 focus groups and 7 interviews. RESULTS: Aboriginal and Torres Strait Islander participants experienced multiple psychosocial stressors at significantly higher rates than non-Indigenous participants. These stressors include diminished access to health care (33%), experiences of racism (34%), grief and sorrow (39%), worry for family (46%), and child welfare experiences (46%). The qualitative findings highlight the cumulative impact of historical, political and social stressors on an already stigmatised population. CONCLUSIONS: The findings of this unique analysis demonstrate the disruptive impact of methamphetamine use on the lives of those who use methamphetamines and their family members. They also illustrate challenges, such as stigma, that may confront those seeking assistance for drug-related issues. Aboriginal and Torres Strait Islander community involvement is necessary to provide support and education for the individual, the family, and the community as a whole. Stigma reduction is therefore a worthy target for intervention.


Assuntos
Povos Aborígenes Australianos e Ilhéus do Estreito de Torres , Qualidade de Vida , Estresse Psicológico , Criança , Humanos , Austrália/epidemiologia , Estudos Transversais , Metanfetamina/efeitos adversos , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Transtornos Relacionados ao Uso de Anfetaminas/terapia , Estigma Social , Aceitação pelo Paciente de Cuidados de Saúde
20.
Addict Biol ; 28(10): e13333, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37753569

RESUMO

Methamphetamine (MA)-induced psychosis (MIP) is associated with increased oxidative toxicity (especially lipid peroxidation) and lowered antioxidant defences. Advanced glycation end products (AGEs) cause oxidative stress upon ligand binding to AGE receptors (RAGEs). There is no data on whether MA use may cause AGE-RAGE stress or whether the latter is associated with MIP. This case-control study recruited 60 patients with MA use disorder and 30 normal controls and measured serum levels of oxidative stress toxicity (OSTOX, lipid peroxidation), antioxidant defences (ANTIOX), magnesium, copper, atherogenicity, AGE and soluble RAGE (sRAGE) and computed a composite reflecting AGE-RAGE axis activity. MA dependence and use were associated with elevated levels of AGE, sRAGE, OSTOX/ANTIOX, Castelli Risk Index 1 and atherogenic index of plasma. Increased sRAGE concentrations were strongly correlated with dependence severity and MA dose. Increased AGE-RAGE stress was correlated with OSTOX, OSTOX/ANTIOX and MA-induced intoxication symptoms, psychosis, hostility, excitement and formal thought disorders. The regression on AGE-RAGE, the OSTOX/ANTIOX ratio, decreased magnesium and increased copper explained 54.8% of the variance in MIP symptoms, and these biomarkers mediated the effects of increasing MA concentrations on MIP symptoms. OSTOX/ANTIOX, AGE-RAGE and insufficient magnesium were found to explain 36.0% of the variance in the atherogenicity indices. MA causes intertwined increases in AGE-RAGE axis stress and oxidative damage, which together predict the severity of MIP symptoms and increased atherogenicity.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Metanfetamina , Transtornos Psicóticos , Humanos , Metanfetamina/efeitos adversos , Antioxidantes , Estudos de Casos e Controles , Cobre , Magnésio , Transtornos Relacionados ao Uso de Anfetaminas/complicações , Estresse Oxidativo
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