Clinical evidences have pointed outthe development of stress-induced substance use disorders.

Our previous findings havedemonstrated that after a single pre-exposure to restraint stress, the basalextracellular levels of glutamate in nucleus accumbens core (NAcore) wereincreased consistent with a decreasedexpression of GLT-1 meanwhile following a cocaine challenge, the glutamatelevels were not increased even more as observed in non-stressed animals,supporting the hypothesis of dysregulation of glutamate homeostasis followingstress. Also, we have shown that the vulnerabilityto cocaine self-administration induced by acute stress was reversed byceftriaxone, a restorer of GLT-1.

This study attempts to determinate the long-termeffect of chronic stress on extracellular levels of glutamate in NAcore, its impact on self-administration behavior, and the roleof glial proteins in the neuropathology of cocaine abuse induced by stress.

Our results indicated that chronic stress inducedsimilar findings to those obtained following acute stress, i.e. a decreasedexpression of GLT-1 meanwhile the glutamate levels following a cocainechallenge were not augmented as observed in control group.

Furthermore, chronic stress induced a facilitation ofthe acquisition of cocaine self-administration and an increase of mRNA levelsof TNF-α and IL-6 inNAcore. Interestingly, minocycline, an inhibitor of microglia activation,reversed both the behavioral response and the increased levels of cytokinesfollowing stress, suggesting a participation of microglia on this phenomenon.

Thus, we propose that glial cells could have apotential role in contributing to the dysregulation of the glutamatehomeostasis in NAcore. These findings constitute a platform to further studieson neurobiological mechanisms underpinning addiction disease.