Glutamatergic systems and memory mechanisms underlying opioid addiction

Glutamate is the main excitatory neurotransmitter in the brain and is of critical importance for the synaptic and circuit mechanisms that underlie opioid addiction. Opioid memories formed over the course of repeated drug use and withdrawal can become powerful stimuli that trigger craving and relapse, and glutamatergic neurotransmission is essential for the formation and maintenance of these memories. In this review, we discuss the mechanisms by which gluta-mate, dopamine, and opioid signaling interact to mediate the primary rewarding effects of opioids, and cover the glutamatergic systems and circuits that mediate the expression, extinc-tion, and reinstatement of opioid seeking over the course of opioid addiction.