Stress-induced vulnerability to cocaine self-administration is reversed by interfering glutamate homeostasis in nucleus accumbens core

AVALOS, M.P.; BOLLATI FLAVIA; GUZMAN A; RIGONI D; CONSTANZA GARCÍA-KELLER; CANCELA LM.

Buenos Aires

Encuentro; Meeting: "The role of glial cells in health and disease of the Nervous System: Clinical and Basic Science walking together"; 2017

Clinical evidences have pointed out the development of stress-induced substance use disorders. Our previous findings have demonstrated that after a single pre-exposure to restraint stress, the basal extracellular levels of glutamate in nucleus accumbens core (NAcore) were increased consistent with a decreased expression of GLT-1, meanwhile following a cocaine challenge, the glutamate levels were not increased even more as observed in non-stressed animals, supporting the hypothesis of dysregulation of glutamate homeostasis following stress. Also, we have shown that the vulnerability to cocaine self-administration induced by acute stress was reversed by ceftriaxone, a restorer of GLT-1.This study attempts to determinate the long-term effect of chronic stress on extracellular levels of glutamate in NAcore, its impact on self-administration behavior, and the role of glial proteins in the neuropathology of cocaine abuse induced by stress.Our results indicated that chronic stress induced similar findings to those obtained following acute stress, i.e. a decreased expression of GLT-1 meanwhile the glutamate levels following a cocaine challenge were not augmented as observed in control group.Furthermore, chronic stress induced a facilitation of the acquisition of cocaine self-administration and an increase of mRNA levels of TNF-α and IL-6 in NAcore. Interestingly, minocycline, an inhibitor of microglia activation, reversed both the behavioral response and the increased levels of cytokines following stress, suggesting a participation of microglia on this phenomenon.Thus, we propose that glial cells could have a potential role in contributing to the dysregulation of the glutamate homeostasis in NAcore. These findings constitute a platform to further studies on neurobiological mechanisms underpinning addiction disease.