Glutamate mechanisms underlying opiate memories

Abstract

As the major excitatory neurotransmitter in the brain, glutamate plays an undisputable integral role in opiate addiction. This relates, in part, to the fact that addiction is a disorder of learning and memory, and glutamate is required for most types of memory formation. As opiate addiction develops, the addict becomes conditioned to engage in addictive behaviors, and these behaviors can be triggered by opiate-associated cues during abstinence, resulting in relapse. Some medications for opiate addiction exert their therapeutic effects at glutamate receptors, especially the NMDA receptor. Understanding the neural circuits controlling opiate addiction, and the locus of glutamate's actions within these circuits, will help guide the development of targeted pharmacotherapeutics for relapse.

Figure 1.

Glutamate systems controlling opiate addiction. Three major glutamatergic inputs to the nucleus accumbens (NAc) arise from the medial prefrontal cortex (mPFC), hippocampus (Hipp), and basolateral amygdala (BLA) and regulate opiate reward and relapse. The BLA also projects to the mPFC and central nucleus of the amygdala (CeA) (see text for details). The CeA can access the ventral tegmental area (VTA) directly or through a relay in the bed nucleus of the stria terminalis (BNST) or periaqueductal gray (PAG). The VTA projects to all components of the circuit and modulates their activity. Output from NAc neurons drives relapse to opiate seeking.