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

VEDELAGO GEORGINA; SANCHEZ, MARIANELA A.; MONGI BRAGATO BETHANIA; AVALOS, MARÍA P.; GUZMÁN, ANDREA S.; BOLLATI, FLAVIA A.; CANCELA, LILIANA M.

Córdoba

Congreso; XXXVI Congreso de la Sociedad Argentina de Neurociencia (Virtual); 2021

SAN

Glia exerts a strong influence on cocaine-induced plasticity, releasing differentmediators that alters excitatory transmission and neuronal signaling. Previousevidence of our lab demonstrated a central role of microglia in the disruption ofglutamate (GLU) homeostasis in the nucleus accumbens (NAc) thought to underliethe stress-induced facilitation of cocaine self-administration. In this project we willevaluate microglia-dependent mechanisms associated to relapse of cocaine seekingbehavior and neurobiological changes. For this purpose, we will use an animalmodel of cocaine self-administration administered with minocycline, (a potentinhibitor of microglia activation), in nanoparticles complexed with chitosan (NP-MINO) to facilitate their bioavailability to the brain. Specifically, we will evaluate theeffect of NP-MINO on cocaine seeking behavior, and associated changes such usmicroglia activation, GLU homeostasis (GLT-1 receptor expression, GLU reuptakeand spillover), structural modifications in dendritic spines and alterations insynaptic plasticity in the NAc. To carry out these objectives, we will use acombination of molecular, neurochemical and behavioral studies. This novel projectwill open new avenues towards the treatment of cocaine addiction. We expect thatby restoring glial function with NP-MINO it will be possible to normalize the changesin GLU homeostasis and synaptic plasticity induced by cocaine and, thus, preventdrug-seeking behavior.