Glutamate receptors and metaplasticity in addiction.

Chronic drug use is a neuroadaptive disorder characterized by strong and persistent plasticity in the mesocorticolimbic reward system. Long-lasting effects of drugs of abuse rely on their ability to hijack glutamate receptor activity and long-term synaptic plasticity processes like long-term potentiation and depression. Importantly, metaplasticity-based modulation of synaptic plasticity contributes to durable neurotransmission changes in mesocorticolimbic pathways including the ventral tegmental area and the nucleus accumbens, causing 'maladaptive' drug memory and higher risk for drug-seeking relapse. On the other hand, drug-induced metaplasticity can make appetitive memories more malleable to modification, offering a potential target mechanism for intervention. Here we review the literature on the role of glutamate receptors in addiction-related metaplasticity phenomena.