Abstract：
: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 the reward 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. Glutamate transporters, such as GLT-1 and xc-, play a key role in maintaining glutamate homeostasis. In preclinical models, agents reversing cocaine-induced decreases in GLT-1 and xc- in the nucleus accumbens attenuate relapse. Very recent studies indicate that other mechanisms of action, such as reversing the mGlu2 receptor downregulation, contribute to these compounds' anti-relapse efficacy. In preclinical models, antagonism of mGlu5 receptors and stimulation of mGlu2/3 autoreceptors 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 effective medication for cocaine use disorder.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Niedzielska-Andres E,Pomierny-Chamioło L,Andres M,Walczak M,Knackstedt LA,Filip M,Przegaliński Edoi
10.1016/j.pharmthera.2020.107797subject
Has Abstractpub_date
2021-01-09 00:00:00pages
107797eissn
0163-7258issn
1879-016Xpii
S0163-7258(20)30328-4journal_volume
221pub_type
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