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

Corticostriatal plasticity, neuronal ensembles, and regulation of drug-seeking behavior.

The idea that interconnected neuronal ensembles code for specific behaviors has been around for decades; however, recent technical improvements allow studying these networks and their causal role in initiating and maintaining behavior. In particular, the role of ensembles in drug-seeking behaviors in the context of addiction is being actively investigated. Concurrent with breakthroughs in quantifying ensembles, research has identified a role for synaptic glutamate spillover during relapse. In particular, the transient relapse-associated changes in glutamatergic synapses on accumbens neurons, as well as in adjacent astroglia and extracellular matrix, are key elements of the synaptic plasticity encoded by drug use and the metaplasticity induced by drug-associated cues that precipitate drug-seeking behaviors. Here, we briefly review the recent discoveries related to ensembles in the addiction field and then endeavor to link these discoveries with drug-induced striatal plasticity and cue-induced metaplasticity toward deeper neurobiological understandings of drug seeking

Corticostriatal plasticity, neuronal ensembles, and regulation of drug-seeking behavior.

The idea that interconnected neuronal ensembles code for specific behaviors has been around for decades; however, recent technical improvements allow studying these networks and their causal role in initiating and maintaining behavior. In particular, the role of ensembles in drug-seeking behaviors in the context of addiction is being actively investigated. Concurrent with breakthroughs in quantifying ensembles, research has identified a role for synaptic glutamate spillover during relapse. In particular, the transient relapse-associated changes in glutamatergic synapses on accumbens neurons, as well as in adjacent astroglia and extracellular matrix, are key elements of the synaptic plasticity encoded by drug use and the metaplasticity induced by drug-associated cues that precipitate drug-seeking behaviors. Here, we briefly review the recent discoveries related to ensembles in the addiction field and then endeavor to link these discoveries with drug-induced striatal plasticity and cue-induced metaplasticity toward deeper neurobiological understandings of drug seeking