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The glutamate system and addiction 

The glutamate system and addiction
The glutamate system and addiction

David J. Nutt

and Liam J. Nestor

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date: 13 June 2021

Glutamate is the primary excitatory neurotransmitter in the brain. Glutamate is involved in synaptic plasticity, particularly within dopamine systems of the brain that are involved in reward. Glutamate-dependent plasticity is involved in the development of substance addiction through its actions at NMDA receptors during long-term potentiation (LTP) related learning and memory processes. This plasticity within brain circuitry involved in learning and memory is sustained during substance abstinence and may provide a neural substrate for a vulnerability to addiction relapse. Medications that possess the efficacy to reduce glutamate tone in certain brain circuits may reduce craving, and ultimately, relapse in substance dependence. Further research is required, however, to show that the modulation of glutamate transmission in the brain confers clinical benefits in substance addiction.

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