Cocaine use disorder: A look at metabotropic glutamate receptors and glutamate transporters

Glutamate transmission is an important mediator of the development of substance use disorders, particularly with regard to relapse. The present review summarizes the changes in glutamate levels in there ward system(the prefrontal cortex, nucleus accumbens, dorsal striatum, hippocampus, and ventral tegmental area) observed in preclinical studies at different stages of cocaine exposure and withdrawal as well as after reinstatement of cocaine-seeking behavior. We also summarize changes in the glutamate transporters xCT and GLT-1 and metabotropic glutamate receptors mGlu2/3, mGlu1, and mGlu5 based on preclinical and clinical studies with an emphasis on their role in cocaine-seeking. Glutamatetransporters,such as GLT-1 and x(c)-, playakeyrole in maintain ingglutamatehomeo stasis. In preclinical models, agents reversing cocaine-induced decreases inGLT-1 and xc- in the nucleus accumbens attenuate relapse. Very recent studies indicate that other mechanism so faction,such as reversing them Glu2 receptor down regulation, contribute to these compounds' anti-relapse efficacy. In preclinical models, antagonis mofm Glu5 receptors and stimulationo fmGlu2/3 auto receptors decrease relapse. Therefore, analysis of the above glutamatergic adaptations seems to be crucial because, so far, there are no prognostic biomarkers that can forecast relapse vulnerability in clinical practice, which would be helpful in alleviating or suppressing this phenomenon. Moreover, these receptor sites can be molecular targets for the development of effectivemedication for cocaine use disorder. (C) 2020 Elsevier Inc. All rights reserved.

Automated summary

This review highlights the significance of glutamate transmission in the development of substance use disorders, particularly in relation to relapse. It discusses the changes in glutamate levels in different brain regions during cocaine exposure, withdrawal, and reinstatement of seeking behavior, as well as the role of glutamate transporters and metabotropic glutamate receptors. The analysis suggests that targeting these glutamatergic adaptations could be crucial for developing effective medications for cocaine use disorder.