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

AVALOS MARIA PAULA; GUZMAN ANDREA SUSANA; RIGONI DAIANA; SANCHEZ MARIANELA ADELA; BOLLATI FLAVIA; CANCELA LILIANA M

Córdoba

Congreso; 2018 Meeting of Argentine Society for Research in Neurosciences; 2018

Sociedad Argentina de Neurociencias

It is well known that repeated exposure to stressful events is one of the most significant risk factors to the development of addiction. Studies from our lab showed that chronic restraint stress induces a facilitation of cocaine self-administration (SA), concomitantly to an alteration of glutamate (GLU) homeostasis and a decrease expression of the GLU transporter, GLT-1, in nucleus accumbens (NA) core. Minocycline, a potent inhibitor of microglia activation, was able to prevent chronic stress-induced facilitation of cocaine SA. The main goal of this study was to evaluate the influence of minocycline on the chronic stress-induced changes on GLU homeostasis and GLT-1 levels. Thus, Wistar rats were exposed to restraint stress 2 hs daily for a week. From day 16 after the 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 were performed to quantified GLT-1 levels by western blot, or GLU levels by HPLC. The GLU dialysate samples were collected from NA core through microdialysis probes in freely-moving rats by the no-net flux technique. Our results pointed out that minocycline prevents the chronic stress-induced increase of basal GLU levels as well as the decrease of GLT-1 levels, in NA core. We propose that microglia can play a key role in the disruption of the GLU homeostasis underlying the chronic stress-induced facilitation of cocaine SA.