Stress and vulnerability to develop cocaine self-administration: restoration of glutamate homeostasis in nucleus accumbens core by minocycline.

AVALOS, MARÍA P.; GUZMAN, ANDREA S.; RIGONI, D.; SANCHEZ MARIANELA ADELA.; BOLLATI, FLAVIA A.; CANCELA, LILIANA M.

Congreso; XXXIII Congreso de la sociedad Argentina de la investigacion en neurociencia; 2018

It is well known that repeated exposure to stressful events is one of the most significant riskfactors to the development of addiction. Studies from our lab showed that chronic restraint stressinduces a facilitation of cocaine self-administration (SA), concomitantly to an alteration ofglutamate (GLU) homeostasis and a decrease expression of the GLU transporter, GLT-1, in nucleusaccumbens (NA) core. Minocycline, a potent inhibitor of microglia activation, was able to preventchronic stress-induced facilitation of cocaine SA. The main goal of this study was to evaluate theinfluence of minocycline on the chronic stress-induced changes on GLU homeostasis and GLT-1levels. Thus, Wistar rats were exposed to restraint stress 2 hs daily for a week. From day 16 afterthe first stress session, all animals were treated with minocycline (30mg/Kg/12hs) or vehicle(DMSO 5%/12 hs) for 5 days. After that, biochemical or neurochemical experiments wereperformed to quantified GLT-1 levels by western blot, or GLU levels by HPLC. The GLU dialysatesamples were collected from NA core through microdialysis probes in freely-moving ratsby the no-net flux technique. Our results pointed out that minocycline prevents the chronicstress-induced increase of basal GLU levels as well as the decrease of GLT-1 levels, in NA core. Wepropose that microglia can play a key role in the disruption of the GLU homeostasis underlying thechronic stress-induced facilitation of cocaine SA.