Chronic Methamphetamine Use Research Articles

Inhibition of RtTg neurons reverses methamphetamine-induced attention deficits

Chronic methamphetamine (METH) use, a prevalent psychostimulant, is known to impair attention, yet the cellular mechanisms driving these deficits remain poorly understood. Here, we employed a rat model of repeated passive METH injections and evaluated attentional performance using the 5-choice serial reaction time task (5-CSRTT). Using single-nucleus RNA sequencing, immunofluorescence and in situ hybridization, we characterized the response of neurons in the reticulotegmental nucleus (RtTg) to METH exposure. Our results indicate that METH exposure disrupts RtTg neurons at the transcriptional level and results in an increased activation ratio of RtTg under 5-CSRTT conditions. Crucially, chemogenetic inactivation of these neurons or RtTg lesion attenuated METH-induced attention deficits, whereas their activation reproduced the deficits. These findings underscore the critical role of RtTg neurons in mediating METH-induced attention deficits, positioning RtTg as a promising therapeutic target for the treatment of attention deficits linked to chronic METH use.

Methamphetamine-related working memory difficulties underpinned by reduced frontoparietal responses.

Working memory difficulties are common, debilitating, and may pose barriers to recovery for people who use methamphetamine. Yet, little is known regarding the neural dysfunctions accompanying these difficulties. Here, we acquired cross-sectional, functional magnetic resonance imaging while people with problematic methamphetamine-use experience (MA+, n =65) and people without methamphetamine-use experience (MA-, n =44) performed a parametric n-back task (0-back through 2-back). Performance on tasks administered outside of the scanner, together with n-back performance, afforded to determine a latent dimension of participants' working memory ability. Behavioural results indicated that MA+ participants exhibited lower scores on this dimension compared to MA- participants (d = -1.39, p < .001). Whole-brain imaging results also revealed that MA+ participants exhibited alterations in load-induced responses predominantly in frontoparietal and default-mode areas. Specifically, while the MA- group exhibited monotonic activation increases within frontoparietal areas and monotonic decreases within default-mode areas from 0-back to 2-back, MA+ participants showed a relative attenuation of these load-induced activation patterns (d = -1.55, p < .001). Moreover, increased activations in frontoparietal areas from 0- to 2-back were related to greater working memory ability among MA+ participants (r = .560, p = .004). No such effects were observed for default-mode areas. In sum, reductions in working memory ability were observed alongside load-induced dysfunctions in frontoparietal and default-mode areas for people with problematic methamphetamine-use experience. Among them, load-induced activations within frontoparietal areas were found to have a strong and specific relationship to individual differences in working memory ability, indicating a putative neural signature of the working memory difficulties associated with chronic methamphetamine use.

Lethal Hemorrhage Following Laparoscopic Cholecystectomy Complicated with Medicolegal Issues

This is a case study of unexpected death after laparoscopic cholecystectomy for acute calculous cholecystitis, complicated with medicolegal issues including chronic methamphetamine use and alleged medicolegal malpractice. The deceased underwent a laparoscopic cholecystectomy following acute calculous cholecystitis, and died on the fourth day after the surgery. Postmortem examination revealed massive peritoneal hemorrhage and the cystic artery on the surgical site was cauterized but unligated. Histopathology of the gallbladder revealed acute inflammation due to gall stones but also ischemic change. As the investigation progressed, a history of chronic methamphetamine use was discovered, however, acute methamphetamine toxicity was excluded by toxicological test. Thus, we suggest forensic considerations based on a review of the literature in the interpretation of the pathology of the gallbladder, the unligated cystic artery and cholecystectomy, and chronic methamphetamine use.

Brain mGlu5 Is Linked to Cognition and Cigarette Smoking but Does Not Differ From Control in Early Abstinence From Chronic Methamphetamine Use.

The group-I metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in methamphetamine exposure in animals and in human cognition. Because people with methamphetamine use disorder (MUD) exhibit cognitive deficits, we evaluated mGlu5 in people with MUD and controls and tested its association with cognitive performance. Positron emission tomography was performed to measure the total VT of [18F]FPEB, a radiotracer for mGlu5, in brains of participants with MUD (abstinent from methamphetamine for at least 2 weeks, N = 14) and a control group (N = 14). Drug use history questionnaires and tests of verbal learning, spatial working memory, and executive function were administered. Associations of VT with methamphetamine use, tobacco use, and cognitive performance were tested. MUD participants did not differ from controls in global or regional VT, and measures of methamphetamine use were not correlated with VT. VT was significantly higher globally in nonsmoking vs smoking participants (main effect, P = .0041). MUD participants showed nonsignificant weakness on the Rey Auditory Verbal Learning Task and the Stroop test vs controls (P = .08 and P = .13, respectively) with moderate to large effect sizes, and significantly underperformed controls on the Spatial Capacity Delayed Response Test (P = .015). Across groups, Rey Auditory Verbal Learning Task performance correlated with VT in the dorsolateral prefrontal cortex and superior frontal gyrus. Abstinent MUD patients show no evidence of mGlu5 downregulation in brain, but association of VT in dorsolateral prefrontal cortex with verbal learning suggests that medications that target mGlu5 may improve cognitive performance.

Can Methamphetamine-Induced Cardiotoxicity be Ameliorated by Aerobic Training and Nutrition Bio-shield Superfood Supplementation in Rats After Withdrawal?

The abuse of methamphetamine is a significant threat to cardiovascular health and has detrimental effects on the myocardium. The present study aims to explore potential interventions that can mitigate myocardial pyroptosis in rats following methamphetamine withdrawal. A total of 104 male Wistar rats were randomly assigned to eight groups. The rats underwent a methamphetamine administration protocol, receiving intraperitoneal injections of 10mg/kg during the 1st week, followed by a weekly dose escalation of 1mg/kg from the second to the 6th week and two times per day. Concurrently, the rats engaged in 6weeks of moderate-intensity treadmill aerobic training, lasting 60min per day, 5days a week. Simultaneously, the Nutrition bio-shield Superfood (NBS) supplement was administered at a dosage of 25g/kg daily for 6weeks. The study assessed the expression levels of Caspase-1, Interleukin-1beta (IL-1β), and Interleukin-18 (IL-18) genes in myocardial tissue. Data analysis utilized a one-way analysis of variance (p ≤ 0.05). The findings revealed that methamphetamine usage significantly elevated the expression of Caspase-1, IL-1β, and IL-18 genes (p ≤ 0.05). Conversely, methamphetamine withdrawal led to a notable reduction in the expression of these genes (p ≤ 0.05). Noteworthy reductions in Caspase-1, IL-1β, and IL-18 expression were observed following aerobic training, supplementation, and the combined approach (p ≤ 0.05). The chronic use of methamphetamine was associated with cardiac tissue damage. This study highlights the potential of aerobic training and NBS Superfood supplementation in mitigating the harmful effects of methamphetamine-induced myocardial pyroptosis. The observed reductions in gene expression levels indicate promising interventions to address the cardiovascular consequences of methamphetamine abuse. The findings of this study suggest that a combination of aerobic exercise and NBS Superfood supplementation can provide a promising approach to mitigate the deleterious effects of methamphetamine on the heart. These findings can be useful for healthcare professionals and policymakers to design effective interventions to prevent and manage the adverse effects of methamphetamine abuse.

Protective effect of melatonin against methamphetamine-induced attention deficits through miR-181/SIRT1 axis in the prefrontal cortex.

Methamphetamine (METH) is an addictive psychostimulant with deleterious effects on the central nervous system. Chronic use of METH in high doses impairs cognition, attention and executive functions, but the underlying mechanisms are still unclear. Sirtuin 1 (SIRT1) is a post-translational regulator that is downregulated following METH neurotoxicity. Melatonin is a neuroprotective hormone that enhances mitochondrial metabolism. Here, we evaluated the effect of melatonin on METH-induced attention deficits disorder and the involvement of the miR-181/SIRT1 axis in melatonin neuroprotection. METH at a dose of 5mg/kg was injected for 21 consecutive days. The animals were assigned to receive either melatonin or the vehicle after METH injections. Attention levels were evaluated with abject-based attention test. In the prefrontal cortex, the expression levels of miR-181a-5p, SIRT1, p53 and CCAR2, as well as the mtDNA copy numbers were evaluated using qRT-PCR and western blotting. The outcomes revealed that melatonin treatment following METH injections improved METH-induced attention deficits. METH toxicity can be associated with changes in the miR-181/SIRT1 axis, elevated levels of p53 and COXII, and decreased levels of mtDNA in the prefrontal cortex of adult rats. Interestingly, administration of melatonin can improve the expression of these molecules and reduces the toxic effects of METH. Melatonin ameliorated the neurotoxicity of METH in the prefrontal cortex and the miR-181/SIRT1 axis is involve in the protective effects of melatonin. However, melatonin can be potentially administrated to improve attention impairment in METH use disorders.

The impact of methamphetamine use and dependence: A systematic review on the cognitive-behavioural implications for road safety

Methamphetamine (MA) users are over-represented in vehicle crash statistics but under-represented in the road safety research literature. This systematic review evaluates the current research base relating to MA use and its associated cognitive-behavioural outcomes; and aims to discuss the implications that these findings may have towards driving and future road safety research directions. Following PRISMA guidelines, a literature search was conducted on research studies using six different databases. Inclusion criteria were acute and chronic MA use in humans, with outcome variables relating to cognitive performance, behavioural tendencies, or psychopathology. Primary exclusion criteria included outcomes that were not directly translatable to road safety outcomes (e.g., health) or very specific samples that may have confounded the effects of MA use (e.g., prisoners). In total, 101 publications met the criteria for inclusion in the review. The literature showed that firstly, acute use (but not abuse) of MA may lead to cognitive enhancements, although these findings are not likely translatable to real-world use. Secondly, evidence suggested that chronic MA use is associated with cognitive impairments, self-regulatory difficulties, and increased aggression, suggesting that MA users may be at a significantly increased risk on the road, in a variety of domains. In addition, chronic MA use has been linked to a range of psychological issues (e.g., psychosis; anxiety; depression), which may exacerbate the negative cognitive-behavioural effects of MA. Finally, abstinence from MA was shown to reduce the aversive impacts of chronic MA use, although cognitive improvements have been demonstrated to take much longer, compared to behavioural and psychopathology conditions. The limitations associated with the current MA literature base were evaluated and methodological suggestions were made for future research to better understand the effect of MA use patterns on driving performance and behaviour.

Efficacy of probiotic supplements in improving the symptoms of psychosis, anxiety, insomnia, and anorexia due to amphetamine and methamphetamine use: a randomized clinical trial.

Changes in the density and diversity of gut microbiota in chronic use of methamphetamine have been mentioned as contributors to psychotic and anxiety symptoms, sleep problems, and loss of appetite. In this placebo-controlled clinical trial, we investigated the effect of the probiotic Lactobacillus Acidophilus in improving psychiatric symptoms among hospitalized patients with chronic methamphetamine use along with psychotic symptoms. 60 inpatients with a history of more than 3 years of methamphetamine use, were randomly assigned to one of two groups receiving either a probiotic capsule or placebo along with risperidone for 8 weeks based on a simple randomization method. In weeks 0, 4, and 8, patients were evaluated using the Brief Psychiatric Rating Scale (BPRS), Beck Anxiety Inventory (BAI), Pittsburgh Sleep Quality Index (PSQI), Simple Appetite Nutritional Questionnaire (SANQ), and Body Mass Index (BMI). Compared to the control group, patients receiving probiotics had better sleep quality, greater appetite, and higher body mass index (there were significant interaction effects of group and time at Week 8 in these variables (t = -3.32, B = -1.83, p = .001, d = 0.89), (t = 10.50, B = 2.65, p <.001, d = 1.25) and (t = 3.40, B = 0.76, p <.001, d = 0.30), respectively. In terms of the improvement of psychotic and anxiety symptoms, there was no statistically significant difference between the two groups. The use of probiotics was associated with improved sleep quality, increased appetite, and increased body mass index in patients with chronic methamphetamine use. Conducting more definitive clinical trials with larger sample sizes and longer-term follow-up of cases is recommended.

Consecutive treatments of methamphetamine promote the development of cardiac pathological symptoms in zebrafish.

Chronic methamphetamine use, a widespread drug epidemic, has been associated with cardiac morphological and electrical remodeling, leading to the development of numerous cardiovascular diseases. While methamphetamine has been documented to induce arrhythmia, most results originate from clinical trials from users who experienced different durations of methamphetamine abuse, providing no documentation on the use of methamphetamine in standardized settings. Additionally, the underlying molecular mechanism on how methamphetamine affects the cardiovascular system remains elusive. A relationship was sought between cardiotoxicity and arrhythmia with associated methamphetamine abuse in zebrafish to identify and to understand the adverse cardiac symptoms associated with methamphetamine. Zebrafish were first treated with methamphetamine 3 times a week over a 2-week duration. Immediately after treatment, zebrafish underwent electrocardiogram (ECG) measurement using an in-house developed acquisition system for electrophysiological analysis. Subsequent analyses of cAMP expression and Ca2+ regulation in zebrafish cardiomyocytes were conducted. cAMP is vital to development of myocardial fibrosis and arrhythmia, prominent symptoms in the development of cardiovascular diseases. Ca2+ dysregulation is also a factor in inducing arrhythmias. During the first week of treatment, zebrafish that were administered with methamphetamine displayed a decrease in heart rate, which persisted throughout the second week and remained significantly lower than the heart rate of untreated fish. Results also indicate an increased heart rate variability during the early stage of treatment followed by a decrease in the late stage for methamphetamine-treated fish over the duration of the experiment, suggesting a biphasic response to methamphetamine exposure. Methamphetamine-treated fish also exhibited reduced QTc intervals throughout the experiment. Results from the cAMP and Ca2+ assays demonstrate that cAMP was upregulated and Ca2+ was dysregulated in response to methamphetamine treatment. Collagenic assays indicated significant fibrotic response to methamphetamine treatment. These results provide potential insight into the role of methamphetamine in the development of fibrosis and arrhythmia due to downstream effectors of cAMP.

Neurological, Behavioral, and Pathophysiological Characterization of the Co-Occurrence of Substance Use and HIV: A Narrative Review.

Combined antiretroviral therapy (cART) has greatly reduced the severity of HIV-associated neurocognitive disorders in people living with HIV (PLWH); however, PLWH are more likely than the general population to use drugs and suffer from substance use disorders (SUDs) and to exhibit risky behaviors that promote HIV transmission and other infections. Dopamine-boosting psychostimulants such as cocaine and methamphetamine are some of the most widely used substances among PLWH. Chronic use of these substances disrupts brain function, structure, and cognition. PLWH with SUD have poor health outcomes driven by complex interactions between biological, neurocognitive, and social factors. Here we review the effects of comorbid HIV and psychostimulant use disorders by discussing the distinct and common effects of HIV and chronic cocaine and methamphetamine use on behavioral and neurological impairments using evidence from rodent models of HIV-associated neurocognitive impairments (Tat or gp120 protein expression) and clinical studies. We also provide a biopsychosocial perspective by discussing behavioral impairment in differentially impacted social groups and proposing interventions at both patient and population levels.

Risk Factors of Suicidal Ideation in Iraqi Crystal Methamphetamine Users.

Crystal methamphetamine, a potent psychostimulant, presents a complex clinical landscape. However, insights into the predisposing factors for suicidal tendencies among Iraqi users remain limited. Our study delves into these risks among 165 patients. Rigorous multivariable analysis was conducted, employing binary logistic regression, drawing from patients from Baghdad Medical City and Ibn-Rushd Teaching Hospital. Most participants were in their third decade (26.62 ± 0.53 years). Regarding suicidal ideation, our model demonstrated robust accuracy, supported by the Hosmer-Lemeshow goodness-of-fit test (NagelKerke's R2 = 0.49, accuracy = 79.4%, p = 0.885). Notably, chronic methamphetamine use exceeding a year (OR = 6.15, p = 0.001), absence of psychological trauma (OR = 4.58, p = 0.006), and incidence of visual hallucinations (OR = 4.52, p = 0.001) rendered users more susceptible to suicidal ideation. Furthermore, our investigation unveiled risk factors tied to psychotic features and withdrawal manifestations. The study underscores pivotal predictors of suicidal ideation, warranting interdisciplinary vigilance from psychiatrists, clinical psychologists, and social workers. By monitoring at-risk individuals, progression toward the intricate spectrum of suicide can be potentially averted. These findings illuminate the urgency of tailored interventions for crystal methamphetamine users, contributing to enhanced holistic care.

NLRP3 inflammasome activation underlies the neuro-oxidative stress associated with Methamphetamine (METH) and SARS-CoV2 induced co-morbidity in human microglia

Abstract Acute and chronic use of Methamphetamine (METH) has critical immunological implications and METH users are more vulnerable to SARS-CoV2 infection. Inflammasomes are activated in response to SARS-CoV2 infection. METH also activates NLRP3 inflammasome in microglia and promotes neuro cognitive deficits. The goal of the study was to examine the involvement of NLRP3 inflammasome in METH and/or SARS-CoV2 induced neuro-oxidative stress in microglial cells. Our results suggests that METH +/− SARS-CoV2 initiated a neuro immune-inflammatory response and mitochondrial oxidative stress via NLRP3 inflammasome activation induced increased Caspase −1 and increased lipid peroxidation. Our data suggests that SARS-CoV2 infection in METH abusing subjects may result in long-term neurological deficits resulting from microglial dysfunction and apoptosis attributed to NLRP3 inflammasome activation.

Prescription psychostimulants as a harm reduction and treatment intervention for methamphetamine use disorder and the implications for nursing clinical practice: A scoping review of the literature.

The global rise in methamphetamine use and its negative effects warrants the need for research exploring harm reduction and treatment interventions for individuals with methamphetamine use disorder. Agonist medications have been utilized for years for the treatment of heroin and opioid addiction, but have yet to be incorporated into mainstream Canadian practice for methamphetamine dependence. This review aims to provide an overview of the current trends of prescription psychostimulant usage for individuals with methamphetamine use disorder from a Canadian perspective, identifies the barriers to accessing prescription psychostimulants for methamphetamine use disorder and highlights the nursing clinical practice implications in caring for individuals with the disorder. Discourse on the sustained abstinence and harm reduction debate is presented from the perspective of methamphetamine abuse is provided along with the neuropsychiatric complications of chronic methamphetamine use. The impacts of specific prescription psychostimulants on cognition are discussed as is the use of neuroimaging techniques to assess neuronal damage in methamphetamine users. Sign of toxicity, overdose and the contraindications for use of these prescription psychostimulants is also presented. The implications to nursing clinical practice in caring for this population is provided, touching on the clinical presentation of methamphetamine use, completing thorough assessment and screening and patient education. The findings of this review indicate the need for further research in this area exploring the benefits of prescription psychostimulants as a harm reduction and treatment intervention for the global problem of methamphetamine dependence.

Neuropathologic Features in Chronic Methamphetamine Use.

Methamphetamine is a psychostimulant that exerts its euphoric and stimulant effects by increasing cytosolic monoamine concentration at the nerve terminal. In addition to its known systemic cardiovascular effects, there is compelling evidence to suggest a direct neurotoxic effect of methamphetamine; however, the existing body of literature includes very few human tissue studies. This exploratory analysis used postmortem human brain specimens to examine histologic and immunohistochemical features associated with chronic methamphetamine use. This retrospective cohort study included 60 decedents who were autopsied at the University of Iowa Hospitals and Clinics between the years 2015 and 2021. Logistic regression models demonstrated no definite pathologic changes in the hippocampi of individuals with a history of chronic methamphetamine use. Decedents with a history of methamphetamine use had a marginally increased odds of basal ganglia arteriosclerosis, which did not reach statistical significance (odds ratio, 3.33; 95% confidence interval, 0.6-19.2; P = 0.17), which may be independent of the systemic hypertensive effects of methamphetamine. Future studies that include targeted examination of brain regions of interest, such as the basal ganglia and specifically the striatum, may prove revealing.

Clinical profile and non-recreational methamphetamine abuse (shabu) among stroke patients in the Philippine population

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. 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. 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. 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.

Differential Effects of Chronic Methamphetamine Treatment on High-Frequency Oscillations and Responses to Acute Methamphetamine and NMDA Receptor Blockade in Conscious Mice.

Dysregulation of high-frequency neuronal oscillations has been implicated in the pathophysiology of schizophrenia. Chronic methamphetamine (METH) use can induce psychosis similar to paranoid schizophrenia. The current study in mice aimed to determine the effect of chronic METH treatment on ongoing and evoked neuronal oscillations. C57BL/6 mice were treated with METH or vehicle control for three weeks and implanted with extradural recording electrodes. Two weeks after the last METH injection, mice underwent three EEG recording sessions to measure ongoing and auditory-evoked gamma and beta oscillatory power in response to an acute challenge with METH (2 mg/kg), the NMDA receptor antagonist MK-801 (0.3 mg/kg), or saline control. A separate group of mice pretreated with METH showed significantly greater locomotor hyperactivity to an acute METH challenge, confirming long-term sensitisation. Chronic METH did not affect ongoing or evoked gamma or beta power. Acute MK-801 challenge reduced ongoing beta power whereas acute METH challenge significantly increased ongoing gamma power. Both MK-801 and METH challenge suppressed evoked gamma power. Chronic METH treatment did not modulate these acute drug effects. There were minor effects of chronic METH and acute METH and MK-801 on selected components of event-related potential (ERP) waves. In conclusion, chronic METH treatment did not exert neuroplastic effects on the regulation of cortical gamma oscillations in a manner consistent with schizophrenia, despite causing behavioural sensitisation.

Cortical thickness and related depressive symptoms in early abstinence from chronic methamphetamine use.

Methamphetamine use is surging globally as a cause of morbidity and mortality. Treatment is typically sought in early abstinence, when craving and depressive symptoms are intense, contributing to relapse and poor outcomes. To advance an understanding of this problem and identify therapeutic targets, we conducted a retrospective analysis of brain structure in 89 adults with Methamphetamine Use Disorder who were in early abstinence and 89 healthy controls. Unlike most prior research, the participants did not significantly differ in age, sex and recent use of alcohol and tobacco (p-values ≥ 0.400). We analysed thickness across the entire cerebral cortex by fitting a general linear model to identify differences between groups. Follow-up regressions were performed to determine whether cortical thickness in regions showing group differences was related to craving, measured on a visual analogue scale, or to the Beck Depression Inventory score. Participants in early methamphetamine abstinence (M ± SD = 22.1 ± 25.6 days) exhibited thinner cortex in clusters within bilateral frontal, parietal, temporal, insular, and right cingulate cortices relative to controls (p-values < 0.001, corrected for multiple comparisons). Unlike craving (β =0.007, p= 0.947), depressive symptoms were positively correlated with cortical thickness across clusters (β =0.239, p = 0.030) and with thickness in the anterior cingulate cluster (β =0.246, p = 0.027) in the methamphetamine-dependent group. Inasmuch as anterior cingulate pathology predicts response to antidepressants for Major Depressive Disorder, cingulate structure may also identify patients with Methamphetamine Use Disorder who can benefit from antidepressant medication.

Effect of High-Intensity Interval Training on Cardiac Apoptosis Markers in Methamphetamine-Dependent Rats.

Chronic methamphetamine use increases apoptosis, leading to heart failure and sudden cardiac death. Previous studies have shown the importance of high-intensity interval training (HIIT) in reducing indices of cardiac tissue apoptosis in different patients, but in the field of sports science, the molecular mechanisms of apoptosis in methamphetamine-dependent rats are still unclear. The present article aimed to investigate the changes in cardiac apoptosis markers in methamphetamine-dependent rats in response to HIIT. Left ventricular tissue was used to evaluate caspase-3, melusin, FAK, and IQGAP1 gene expression. Rats were divided into four groups: sham, methamphetamine (METH), METH-control, and METH-HIIT. METH was injected for 21 days and then the METH-HIIT group performed HIIT for 8 weeks at 5 sessions per week. The METH groups showed increased caspase-3 gene expression and decreased melusin, FAK, and IQGAP1 when compared to the sham group. METH-HIIT showed decreased caspase-3 and increased melusin and FAK gene expression compared with the METH and METH-control groups. The IQGAP1 gene was higher in METH-HIIT when compared with METH, while no difference was observed between METH-HIIT and METH-control. Twenty-one days of METH exposure increased apoptosis markers in rat cardiac tissue; however, HIIT might have a protective effect, as shown by the apoptosis markers.

Disruption of regional homogeneity in the brains of chronic methamphetamine users.

Previous studies have reported evidence supporting structural and functional alterations in the brains of methamphetamine (MA) users. The aim of the present study was to extend current knowledge regarding brain function(s) in MA users by examining regional homogeneity (ReHo).Chronic MA users (51 male, 46 female), who were undergoing supervised abstinence for 12 to 621 days, and 79 healthy controls (43 male, 36 female) underwent resting-state functional brain magnetic resonance imaging. Voxel-wise whole-brain scale group differences in ReHo were examined. The mean ReHo values of significant clusters were extracted, and linear regression was used to identify factors that contributed to these mean ReHo values.MA users exhibited lower ReHo values in the left orbital part of the inferior frontal gyrus extending to the left insula and left temporal pole, left amygdala, and left fusiform gyrus. MA users also exhibited greater ReHo values in the bilateral pre- and postcentral gyri and right cerebellum. Characteristics of MA use, including duration, duration of abstinence from MA, and age at onset of MA use, demonstrated no reliable contribution to ReHo of the significant clusters.Findings of the present study demonstrated that chronic MA use was associated with regional specific disruption of ReHo, which is relatively independent of structural and functional alterations and, apparently, does not recover after relatively long-term abstinence. This disruption may underlie overall neurocognitive deficits in MA users, which is difficult to recover.

A comprehensive study to delineate the role of an extracellular vesicle-associated microRNA-29a in chronic methamphetamine use disorder.

Extracellular vesicles (EVs), which express a repertoire of cargo molecules (cf. proteins, microRNA, lipids, etc.), have been garnering a prominent role in the modulation of several cellular processes. Here, using both non‐human primate and rodent model systems, we provide evidence that brain‐derived EV (BDE) miRNA, miR‐29a‐3p (mir‐29a), is significantly increased during chronic methamphetamine (MA) exposure. Further, miR‐29a levels show significant increase both with drug‐seeking and reinstatement in a rat MA self‐administration model. We also show that EV‐associated miR‐29a is enriched in EV pool comprising of small EVs and exomeres and further plays a critical role in MA‐induced inflammation and synaptodendritic damage. Furthermore, treatment with the anti‐inflammatory drug ibudilast (AV411), which is known to reduce MA relapse, decreased the expression of miR‐29a and subsequently attenuated inflammation and rescued synaptodendritic injury. Finally, using plasma from MUD subjects, we provide translational evidence that EV‐miR29a could potentially serve as a biomarker to detect neuronal damage in humans diagnosed with MA use disorder (MUD). In summary, our work suggests that EV‐associated miR‐29a‐3p plays a crucial role in MUD and might be used as a potential blood‐based biomarker for detecting chronic inflammation and synaptic damage.