Microglia-dependent glutamatergic mechanisms in the nucleus accumbens core mediate chronic stress-induced vulnerability to developing cocaine self-administration

MARIA PAULA AVALOS; ANDREA GUZMAN; DAIANA RIGONI; EZEQUIEL GOROSTIZA; MARIANELA SANCHEZ; BETHANIA MONGI-BRAGATO; CONSTANZA GARCIA KELLER; EDUARDO PERASSI; MIRIAM VIRGOLINI; LILIANA CANCELA

BRAIN BEHAVIOR AND IMMUNITY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2022

0889-1591

tressful experience-induced cocaine-related behaviors are associated with a significant impairment of glutamatergic mechanisms in the Nucleus Accumbens core (NAcore). The hallmarks of disrupted glutamate homeostasis following restraint stress are the enduring imbalance of glutamate efflux after a cocaine stimulus and increased basal concentrations of extracellular glutamate attributed to GLT-1 downregulation in the NAcore. Glutamate transmission is tightly linked to microglia functioning. However, the role of microglia in the biological basis of stress-induced addictive behaviors is still unknown. By using minocycline, a potent inhibitor of microglia activation with anti-inflammatory properties, we determined whether microglia could aid chronic restraint stress (CRS)-induced glutamate homeostasis disruption in the NAcore, underpinning stress-induced cocaine self-administration. In this study, adult male rats were restrained for 2 h/day for seven days (day 1-7). From day 16 until compl