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

Jessica Moretti,Jennifer Rodger,Eugenia Z Poh

doi:10.3389/fnins.2020.00137

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.

Highlights

Substance dependence is a chronic, relapsing disorder with significant monetary and societal costs
The aim of this review is to highlight the rationale and potential for repetitive transcranial magnetic stimulation (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
One avenue of investigation is the use of non-invasive brain stimulation techniques, such as repetitive transcranial magnetic stimulation. rTMS therapy has been Food and Drug Administration (FDA) approved for treatment-resistant depression (O’Reardon et al, 2007; Horvath et al, 2010) and obsessive-compulsive disorder (Carmi et al, 2018) and has shown promise in several other neurological disorders where its ability to induce plasticity proves useful (Fregni and PascualLeone, 2007; Pell et al, 2011; Lefaucheur et al, 2014)

Summary

INTRODUCTION

Substance dependence is a chronic, relapsing disorder with significant monetary and societal costs. Control experiments should include a viral construct that does not encode for lightsensitive ion channels (Yizhar et al, 2011; Owen et al, 2019) Despite these limitations, a study has shown that optogenetics stimulation of hypoactive glutamatergic neurons of the PFC can modulate compulsive drug seeking in cocaine-addicted rats (Chen et al, 2013). An increasing number of studies have shown anticraving effects following rTMS treatment targeting the PFC (see Ma et al, 2019; Madeo and Bonci, 2019; Zhang et al, 2019), presumably through modulation of the efferent glutamatergic and afferent dopaminergic connections (Diana, 2011; Diana et al, 2017; Figure 1). A recent review of rTMS literature has suggested that the best predictor of rTMS-induced plasticity is pulse frequency (Wilson and St George, 2016); we have structured the studies by frequency of stimulation below

Hz or Greater

Hz or Less

Findings

SUMMARY