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

• Grant number: 19/23454-3
• Support Opportunities: Research Grants - Visiting Researcher Grant - International
• Duration: July 01, 2020 - May 29, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Fabio Cardoso Cruz
• Grantee: Fabio Cardoso Cruz
• Visiting researcher: Vincent Vialou
• Visiting researcher institution: Institut National de la Santé et de la Recherche Médicale (Inserm), France
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 18/15505-4 - Neurobiology study of relapse to alcohol and cocaine seeking: identification of plasticity in neuronal ensembles that encodes addiction-related memories, AP.JP2

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)