Role of glutamatergic system and mesocorticolimbic circuits in alcohol dependence


Emerging evidence demonstrates that alcohol dependence is associated with dysregulation of several neurotransmitters. Alterations in dopamine, glutamate and gamma-aminobutyric acid release are linked to chronic alcohol exposure. The effects of alcohol on the glutamatergic system in the mesocorticolimbic areas have been investigated extensively. Several studies have demonstrated dysregulation in the glutamatergic systems in animal models exposed to alcohol. Alcohol exposure can lead to an increase in extracellular glutamate concentrations in mesocorticolimbic brain regions. In addition, alcohol exposure affects the expression and functions of several glutamate receptors and glutamate transporters in these brain regions. In this review, we discussed the effects of alcohol exposure on glutamate receptors, glutamate transporters and glutamate homeostasis in each area of the mesocorticolimbic system. In addition, we discussed the genetic aspect of alcohol associated with glutamate and reward circuitry. We also discussed the potential therapeutic role of glutamate receptors and glutamate transporters in each brain region for the treatment of alcohol dependence. Finally, we provided some limitations on targeting the glutamatergic system for potential therapeutic options for the treatment alcohol use disorders.