Minocycline loaded chitosan nanoparticles for the prevention of relapse to cocaine seeking in a self-administration model

VEDELAGO, G.; SANCHEZ, M. A.; MONGI BRAGATO, B; GUZMAN, A.S.; AVALOS, M.P.; BOLLATI, F.; CANCELA, L. M.

Congreso; XXXVI Congreso anual (virtual) de la 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 (NPMINO) to facilitate their bioavailability to the 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.