The role of matricellular protein hevin in cocaine reward effects in mice

Abstract

Matricellular proteins mediate interaction between cells and the extracellular matrix and are essential regulators of synaptic function and architecture. Recently, the two prototypical matricellular proteins SPARC and hevin have been implicated in depression-like behaviors, antidepressant response and resilience to stress. Studies show that hevin is induced by chronic social stress in the nucleus accumbens (NAc), a key brain reward region, only in resilient individuals. Importantly, its overexpression in susceptible mice could reverse social avoidance. This key observation, along with other evidence supporting a role for hevin in synaptogenesis and its presence at excitatory synapses, suggests that hevin is involved in the neuroplasticity underlying positive affect and motivation. Addictive behavior is emotional in nature and closely linked not only to reward mechanisms but also to stress, anxiety, and coping. Furthermore, the NAc plays an essential role in regulating the motivation and the rewarding properties of drugs of abuse. Based on these considerations, we propose to combine rodent behavior, neuroanatomy, pharmacology, molecular biology and viral-mediated gene transfer to unravel the role of hevin on the rewarding and motivation properties of drugs of abuse in vivo. (AU)