Dynamic regulation of the extracellular matrix in reward memory processes: a question of time

Abstract

Substance use disorders are a global health problem with increasing prevalence resulting in significant socioeconomic burden and increased mortality. Converging lines of evidence point to a critical role of brain extracellular matrix (ECM) molecules in the pathophysiology of substance use disorders. An increasing number of preclinical studies highlight the ECM as a promising target for development of novel cessation pharmacotherapies. The brain ECM is dynamically regulated during learning and memory processes, thus the time course of ECM alterations in substance use disorders is a critical factor that may impact interpretation of the current studies and development of pharmacological therapies. This review highlights the evidence for the involvement of ECM molecules in reward learning, including drug reward and natural reward such as food, as well as evidence regarding the pathophysiological state of the brain’s ECM in substance use disorders and metabolic disorders. We focus on the information regarding time-course and substance specific changes in ECM molecules and how this information can be leveraged for the development of therapeutic strategies.

Extracellular matrix abnormalities in the hippocampus of subjects with substance use disorder

“…PNNs contribute to synaptic homeostasis through the stabilization of synapses and PVB interneuron-mediated excitatory/inhibitory balance [ 70 ]. Thus, PNNs may stabilize synapses involved in drug reward processes that contribute to context-induced relapse [ 18 ].…”

“…Contextual cues associated with drug use are a critical factor contributing to relapse in individuals with SUD and highlight the strength of memory circuits associated with reward processing [ 3 – 7 ]. A growing number of studies indicate a critical role of extracellular matrix molecules (ECM) in the regulation of reward memories [ 8 – 17 ] (for reviews see [ 18 , 19 ]). Recent gene expression profiling studies demonstrate altered expression of pathways involved in ECM regulation in the dorsolateral prefrontal cortex and nucleus accumbens of subjects with opioid use disorder (OUD) [ 12 , 20 ] as well as in preclinical models of OUD [ 20 ].…”