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RTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders.

ABSTRACT: Cocaine use disorder and methamphetamine use disorder are chronic, relapsing disorders with no US Food and Drug Administration-approved interventions. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool that has been increasingly investigated as a possible therapeutic intervention for substance use disorders. rTMS may have the ability to induce beneficial neuroplasticity in abnormal circuits and networks in individuals with addiction. The aim of this review is to highlight the rationale and potential for rTMS to treat cocaine and methamphetamine dependence: we synthesize the outcomes of studies in healthy humans and animal models to identify and understand the neurobiological mechanisms of rTMS that seem most involved in addiction, focusing on the dopaminergic and glutamatergic systems. rTMS-induced changes to neurotransmitter systems include alterations to striatal dopamine release and metabolite levels, as well as to glutamate transporter and receptor expression, which may be relevant for ameliorating the aberrant plasticity observed in individuals with substance use disorders. We also discuss the clinical studies that have used rTMS in humans with cocaine and methamphetamine use disorders. Many such studies suggest changes in network connectivity following acute rTMS, which may underpin reduced craving following chronic rTMS. We suggest several possible future directions for research relating to the therapeutic potential of rTMS in addiction that would help fill current gaps in the literature. Such research would apply rTMS to animal models of addiction, developing a translational pipeline that would guide evidence-based rTMS treatment of cocaine and methamphetamine use disorder.

SUBMITTER: Moretti J

PROVIDER: S-EPMC7068681 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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rTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders.

Moretti Jessica J Poh Eugenia Z EZ Rodger Jennifer J

Frontiers in neuroscience 20200306

Cocaine use disorder and methamphetamine use disorder are chronic, relapsing disorders with no US Food and Drug Administration-approved interventions. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool that has been increasingly investigated as a possible therapeutic intervention for substance use disorders. rTMS may have the ability to induce beneficial neuroplasticity in abnormal circuits and networks in individuals with addiction. The aim of this revi ...[more]

PMID: 32210744

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Project description:ImportanceStimulant use disorder is common, affecting between 0.3% and 1.1% of the population, and costs more than $85 billion per year globally. There are no licensed treatments to date. Several lines of evidence implicate the dopamine system in the pathogenesis of substance use disorder. Therefore, understanding the nature of dopamine dysfunction seen in stimulant users has the potential to aid the development of new therapeutics.ObjectiveTo comprehensively review the in vivo imaging evidence for dopaminergic alterations in stimulant (cocaine, amphetamine, or methamphetamine) abuse or dependence.Data sourcesThe entire PubMed, EMBASE, and PsycINFO databases were searched for studies from inception date to May 14, 2016.Study selectionCase-control studies were identified that compared dopaminergic measures between stimulant users and healthy controls using positron emission tomography or single-photon emission computed tomography to measure striatal dopamine synthesis or release or to assess dopamine transporter availability or dopamine receptor availability.Data extraction and synthesisDemographic, clinical, and imaging measures were extracted from each study, and meta-analyses and sensitivity analyses were conducted for stimulants combined, as well as for cocaine and for amphetamine and methamphetamine separately if there were sufficient studies.Main outcomes and measuresDifferences were measured in dopamine release (assessed using change in the D2/D3 receptor availability after administration of amphetamine or methylphenidate), dopamine transporter availability, and dopamine receptor availability in cocaine users, amphetamine and methamphetamine users, and healthy controls.ResultsA total of 31 studies that compared dopaminergic measures between 519 stimulant users and 512 healthy controls were included in the final analysis. In most of the studies, the duration of abstinence varied from 5 days to 3 weeks. There was a significant decrease in striatal dopamine release in stimulant users compared with healthy controls: the effect size was -0.84 (95% CI, -1.08 to -0.60; P < .001) for stimulants combined and -0.87 (95% CI, -1.15 to -0.60; P < .001) for cocaine. In addition, there was a significant decrease in dopamine transporter availability: the effect size was -0.91 (95% CI, -1.50 to -0.32; P < .01) for stimulants combined and -1.47 (95% CI, -1.83 to -1.10; P < .001) for amphetamine and methamphetamine. There was also a significant decrease in D2/D3 receptor availability: the effect size was -0.76 (95% CI, -0.92 to -0.60; P < .001) for stimulants combined, -0.73 (95% CI, -0.94 to -0.53; P < .001) for cocaine, and -0.81 (95% CI, -1.12 to -0.49; P < .001) for amphetamine and methamphetamine. Consistent alterations were not found in vesicular monoamine transporter, dopamine synthesis, or D1 receptor studies.Conclusions and relevanceData suggest that both presynaptic and postsynaptic aspects of the dopamine system in the striatum are down-regulated in stimulant users. The commonality and differences between these findings and the discrepancies with the preclinical literature and models of drug addiction are discussed, as well as their implications for future drug development.

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Project description:BACKGROUND:Methamphetamine is considered more dangerous than other stimulants because of its acute complications, long-term neurotoxicity, and potential for drug dependence. Until now, there have been no evidence-based guidelines for the treatment of methamphetamine-related disorders, either in Germany or abroad. METHODS:A systematic literature search was performed on the treatment of methamphetamine-related disorders. Based on this literature review, a multidisciplinary expert panel developed recommendations using the nominal group technique. RESULTS:The evidence base for the treatment of methamphetamine-related disorders is sparse. The efficacy of psychotherapeutic techniques such as cognitive behavioral therapy and contingency management and the efficacy of complex, disorder-specific treatment programs have been proven in ran - domized controlled trials, but it remains unclear which method is best. Persons carrying a diagnosis of substance abuse should be offered psychotherapy. Structured exercise programs, whether self-directed or professionally led, can improve addiction-specific endpoints as well as comorbid disorders and should, therefore, be offered as well. Pharmacotherapy has shown little to no effect in relatively low-quality clinical trials with low case numbers and high dropout rates, and therefore only a few weak recommendations were made. These include tranquilizers for the short-term treatment of agitation and atypical antipsychotics if necessary. Attempts to substitute other substances, such as methylphenidate or dexamphetamine, for methamphetamine have not yielded any robust evidence to date. Sertraline should not be administered due to serious adverse events. CONCLUSION:Many of the recommendations in the guideline are made with a weak grade of recommendation because of the poor evidence base and the modest size of the reported therapeutic effects. In acute situations, symptomoriented treatment is recommended. Psychotherapy and exercise should be offered as well.

Dataset Information

RTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders.

Publications

rTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders.

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