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

Grant number: 19/23454-3
Support type:Research Grants - Visiting Researcher Grant - International
Duration: July 01, 2020 - August 01, 2020
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
Home 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)