Methamphetamine Induces Systemic Inflammation and Anxiety: The Role of the Gut–Immune–Brain Axis

Davidson, Majid; Mayer, M; Habib, Amanda; Rashidi, Niloufar; Filippone, Rhiannon T; Fraser, Sarah; Prakash, Monica D.; Sinnayah, Puspha; Tangalakis, Kathy; Mathai, Michael L.; Nurgali, Kulmira; Apostolopoulos, Vasso

doi:10.3390/ijms231911224

Cited by 17 publications

(12 citation statements)

References 101 publications

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“…Floating neurospheres were formed and pelleted by centrifuging at 200 g for 5 min after 2 days of culturing. Previous observations suggest a time/dose-dependent effect of METH on the brain ( Davidson et al, 2022 ). Due to the timeline of neurosphere proliferation and differentiation, it was challenging to expose METH at low concentrations for a longer period in order to generate toxicity ( Lenzi et al, 2022 ).…”

Section: Methodsmentioning

confidence: 93%

Methamphetamine exposure drives cell cycle exit and aberrant differentiation in rat hippocampal-derived neurospheres

Wang,

et al. 2023

Front. Pharmacol.

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Introduction: Methamphetamine (METH) abuse by pregnant drug addicts causes toxic effects on fetal neurodevelopment; however, the mechanism underlying such effect of METH is poorly understood.Methods: In the present study, we applied three-dimensional (3D) neurospheres derived from the embryonic rat hippocampal tissue to investigate the effect of METH on neurodevelopment. Through the combination of whole genome transcriptional analyses, the involved cell signalings were identified and investigated.Results: We found that METH treatment for 24 h significantly and concentration-dependently reduced the size of neurospheres. Analyses of genome-wide transcriptomic profiles found that those down-regulated differentially expressed genes (DEGs) upon METH exposure were remarkably enriched in the cell cycle progression. By measuring the cell cycle and the expression of cell cycle-related checkpoint proteins, we found that METH exposure significantly elevated the percentage of G0/G1 phase and decreased the levels of the proteins involved in the G1/S transition, indicating G0/G1 cell cycle arrest. Furthermore, during the early neurodevelopment stage of neurospheres, METH caused aberrant cell differentiation both in the neurons and astrocytes, and attenuated migration ability of neurospheres accompanied by increased oxidative stress and apoptosis.Conclusion: Our findings reveal that METH induces an aberrant cell cycle arrest and neuronal differentiation, impairing the coordination of migration and differentiation of neurospheres.

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Section: Methodsmentioning

confidence: 93%

Methamphetamine exposure drives cell cycle exit and aberrant differentiation in rat hippocampal-derived neurospheres

Wang,

et al. 2023

Front. Pharmacol.

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“…This approach has garnered attention due to its versatility and potential to bring about structural modifications in a range of compounds that can target various drugs or even combinations of drugs [ 34 , 35 , 36 ]. The primary objective of these adjustments is to encourage the generation of potent antibody responses, a key element in the effectiveness of vaccination initiatives [ 37 , 38 ]. Conjugate vaccines have shown great promise as an immunotherapeutic intervention strategy for SUDs.…”

Section: Conjugate Vaccinesmentioning

confidence: 99%

Vaccines to Treat Substance Use Disorders: Current Status and Future Directions

Lu,

Li,

Zheng

et al. 2024

Pharmaceutics

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Addiction, particularly in relation to psychostimulants and opioids, persists as a global health crisis with profound social and economic ramifications. Traditional interventions, including medications and behavioral therapies, often encounter limited success due to the chronic and relapsing nature of addictive disorders. Consequently, there is significant interest in the development of innovative therapeutics to counteract the effects of abused substances. In recent years, vaccines have emerged as a novel and promising strategy to tackle addiction. Anti-drug vaccines are designed to stimulate the immune system to produce antibodies that bind to addictive compounds, such as nicotine, cocaine, morphine, methamphetamine, and heroin. These antibodies effectively neutralize the target molecules, preventing them from reaching the brain and eliciting their rewarding effects. By obstructing the rewarding sensations associated with substance use, vaccines aim to reduce cravings and the motivation to engage in drug use. Although anti-drug vaccines hold significant potential, challenges remain in their development and implementation. The reversibility of vaccination and the potential for combining vaccines with other addiction treatments offer promise for improving addiction outcomes. This review provides an overview of anti-drug vaccines, their mechanisms of action, and their potential impact on treatment for substance use disorders. Furthermore, this review summarizes recent advancements in vaccine development for each specific drug, offering insights for the development of more effective and personalized treatments capable of addressing the distinct challenges posed by various abused substances.

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“…METH is an amine drug that is abused due to its sympathomimetic effects and is taken via inhalation, ingestion, injection, or smoking [49,50]. METH is a weak lipophilic base that diffuses across the plasmalemma of the presynaptic neurons and vesicular membranes [51].…”

Section: Tryptophan and Its Metabolitesmentioning

confidence: 99%

Tryptophan and Substance Abuse: Mechanisms and Impact

Davidson

Rashidi

Hossain

et al. 2023

IJMS

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Addiction, the continuous misuse of addictive material, causes long-term dysfunction in the neurological system. It substantially affects the control strength of reward, memory, and motivation. Addictive substances (alcohol, marijuana, caffeine, heroin, methamphetamine (METH), and nicotine) are highly active central nervous stimulants. Addiction leads to severe health issues, including cardiovascular diseases, serious infections, and pulmonary/dental diseases. Drug dependence may result in unfavorable cognitive impairments that can continue during abstinence and negatively influence recovery performance. Although addiction is a critical global health challenge with numerous consequences and complications, currently, there are no efficient options for treating drug addiction, particularly METH. Currently, novel treatment approaches such as psychological contingency management, cognitive behavioral therapy, and motivational enhancement strategies are of great interest. Herein, we evaluate the devastating impacts of different addictive substances/drugs on users′ mental health and the role of tryptophan in alleviating unfavorable side effects. The tryptophan metabolites in the mammalian brain and their potential to treat compulsive abuse of addictive substances are investigated by assessing the functional effects of addictive substances on tryptophan. Future perspectives on developing promising modalities to treat addiction and the role of tryptophan and its metabolites to alleviate drug dependency are discussed.

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Methamphetamine Induces Systemic Inflammation and Anxiety: The Role of the Gut–Immune–Brain Axis

Cited by 17 publications

References 101 publications

Methamphetamine exposure drives cell cycle exit and aberrant differentiation in rat hippocampal-derived neurospheres

Methamphetamine exposure drives cell cycle exit and aberrant differentiation in rat hippocampal-derived neurospheres

Vaccines to Treat Substance Use Disorders: Current Status and Future Directions

Tryptophan and Substance Abuse: Mechanisms and Impact

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