Minocycline loaded chitosan nanoparticles for the prevention of relapse to cocaine seeking in a selfadministration model

VEDELAGO GEORGINA; SANCHEZ MARIANELA ADELA; MONGI-BRAGATO, BETHANIA; GUZMAN ANDREA SUSANA; AVALOS MARIA PAULA; BOLLATI FLAVIA; CANCELA LILIANA M

Cordoba

Congreso; Sociedad Argentina de Investigación en neurociencias; 2021

Sociedad Argentina de Investigación en neurociencias

Glia exerts a strong influence on cocaine-induced plasticity, releasing different mediators that alters excitatory transmission and neuronal signaling. Previous evidence of our lab demonstrated a central role of microglia in the disruption of glutamate (GLU) homeostasis in the nucleus accumbens (NAc) thought to underlie the stress induced facilitation of cocaine self-administration. In this project we will evaluate microglia-dependent mechanisms associated to relapse of cocaine seeking behavior and neurobiological changes. For this purpose, we will use an animal model of cocaine self-administration administered with minocycline, (a potent inhibitor of microglia activation), in nanoparticles complexed with chitosan (NP-MINO) to facilitate their bioavailability tothe brain. Specifically, we will evaluate the effect of NP-MINO on cocaine seeking behavior, and associated changes such us microglia activation, GLU homeostasis (GLT-1 receptor expression, GLU reuptake and spillover), structural modifications in dendritic spines and alterations in synaptic plasticity in the NAc. To carry out these objectives, we will use a combination of molecular, neurochemical and behavioral studies. This novel project will open new avenues towards the treatment of cocaine addiction. We expect that by restoring glial function with NP-MINO it will be possible to normalize the changes in GLU homeostasis and synaptic plasticity induced by cocaine and, thus, prevent drug-seeking behavior.