Minocycline prevents chronic restraint stress-induced vulnerability to developing cocaine self-administration and associated glutamatergic mechanisms: a potential role of microglia

AVALOS, MARÍA PAULA; GUZMAN, ANDREA SUSANA; RIGONI, DAIANA; GOROSTIZA, EZEQUIEL AXEL; SANCHEZ, MARIANELA ADELA; MONGI-BRAGATO, BETHANIA; GARCIA-KELLER, CONSTANZA; PERASSI, EDUARDO MARCELO; VIRGOLINI, MIRIAM BEATRIZ; PERALTA RAMOS, JAVIER MARÍA; IRIBARREN, PABLO; CALFA, GASTÓN DIEGO; BOLLATI, FLAVIA ANDREA; CANCELA, LILIANA MARINA

BRAIN BEHAVIOR AND IMMUNITY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2022 vol. 101 p. 359 - 359

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