Structural remodelling of microglia and dendritic spines in the Nucleus Accumbens core underlie chronic restraint stress-induced cocaine sensitization

AVALOS M. P.; BETHANIA MONGI BRAGATO; MARIANELA ADELA SANCHEZ; GOROSTIZA A.E; CALFA, G; RIGONI D.; GUZMAN A.S; BOLLATI F.; CANCELA LILIANA M

Córdoba

Congreso; XXXV CONGRESO ANUAL DE LA SOCIEDAD ARGENTINA DE NEUROCIENCIA (VIRTUAL); 2020

SAN

Stress has long been known to increase vulnerability to drug addiction. Studies from our lab showed that stressful experience causes enduring neuroadaptations on glutamate system in the Nucleus Accumbens (NAc) which enables sensitized response to cocaine. Similarly, we evidenced glutamate mechanisms implied in psychostimulant sensitization induced effects at immune level. However, there is no evidence of the role played by microglia in this phenomenon. Here we evaluate the effect of minocycline (MNC), an inhibitor of microglia activation, on stress-induced cocaine sensitization, morphological changes of microglia and postsynaptic structural modifications in the NAc core. Rats were exposed to restraint stress (2 h/day x 7 days) and treated with MNC (30 mg/Kg/12h) or vehicle for 5 days previous cocaine (15 mg/kg) or saline challenge administration (Day 21). On this day, locomotor activity, NA immunofluorescence for iba-1 (microglia marker) and dendritic staining with a lipophilic dye (Dil) were performed. MNC was able to prevent stress-induced cocaine sensitization and stress-induced hyper-ramification of accumbal microglia. In parallel, stress-induced postsynaptic structural remodelling were reversed with MNC by reorganizing the density of each spine type. These results reveal a critical role of microglia in postsynaptic structural adaptations following stress to trigger cocaine sensitization and demonstrates promising evidence of MNC as therapy to prevent this comorbidity.