Releasing Addiction Memories Trapped in Perineuronal Nets.

Drug addiction can be conceptualized at a basic level as maladaptive learning and memory. Addictive substances elicit changes in brain circuitry involved in reward, cognition, and emotional state, leading to the formation and persistence of strong drug-associated memories that lead to craving and relapse. Recently, perineuronal nets (PNNs), extracellular matrix (ECM) structures surrounding neurons, have emerged as regulators of learning, memory, and addiction behaviors. PNNs do not merely provide structural support to neurons but are dynamically remodeled in an experience-dependent manner by metalloproteinases. They function in various brain regions through constituent proteins such as brevican that are implicated in neural plasticity. Understanding the function of PNN components in memory processes may lead to new therapeutic approaches to treating addiction.