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Published on: May 3, 2017
Using glutamate homeostasis as a target for treating addictive disorders
Kathryn J Reissner1, Peter W Kalivas
1Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina, USA.
Behavioural Pharmacology
|July 17, 2010
Summary
Disruptions in glutamate homeostasis, particularly involving the cystine/glutamate exchanger (xc(-)) and glial glutamate transporter (GLT-1), are linked to addiction. Targeting these systems can restore glutamate balance and reduce drug-seeking behaviors.
Area of Science:
- Neuroscience
- Molecular Biology
- Addiction Research
Background:
- Cellular mechanisms maintain glutamate homeostasis and regulate extrasynaptic glutamate levels.
- Disruptions in glutamate homeostasis are increasingly linked to addictive disorders.
- Prolonged drug exposure alters key homeostatic components like the cystine/glutamate exchanger (xc(-)) and glial glutamate transporter (EAAT2/GLT-1).
Purpose of the Study:
- To review evidence linking impaired glutamate homeostasis to long-term drug-seeking behaviors.
- To examine how neuroadaptations in xc(-) and GLT-1 disrupt glutamate homeostasis.
- To explore the potential of targeting these components for addiction treatment.
Main Methods:
- Review of existing scientific literature on glutamate homeostasis and addiction.
- Analysis of neuroadaptations in glutamate transport systems (xc(-) and GLT-1).
- Discussion of the impact on synaptic and extrasynaptic glutamate signaling.
Main Results:
- Impaired glutamate homeostasis is a critical mediator of long-term drug-seeking behaviors.
- Chronic neuroadaptations in xc(-) and GLT-1 contribute to disrupted glutamate homeostasis.
- Altered synaptic and extrasynaptic glutamate levels influence receptor signaling, synaptic plasticity, and circuit activity.
Conclusions:
- Targeting the cystine/glutamate exchanger (xc(-)) and the glial glutamate transporter (GLT-1) can restore glutamate homeostasis.
- Restoring glutamate balance shows potential for inhibiting drug-seeking behaviors.
- Understanding these mechanisms offers novel therapeutic strategies for addiction.
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