{"id":"CONICETDig_07fd2e84bafe0dcec7a0a9d9b320335c","dc:title":"Minocycline prevents chronic restraint stress-induced vulnerability to developing cocaine self-administration and associated glutamatergic mechanisms: a potential role of microglia","dc:creator":"Cancela, Liliana Marina","dc:date":"2024","dc:description":["Stressful 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\u2013induced cocaine self-administration. In this study, adult male rats were restrained for 2 h\/day for seven days (day 1\u20137). From day 16 until completing the experimental protocol, animals received a vehicle or minocycline treatment (30 mg\/Kg\/12h i.p.). On day 21, animals were assigned to microscopic, biochemical, neurochemical or behavioral studies. We confirm that the CRS-induced facilitation of cocaine self-administration is associated with enduring GLT-1 downregulation, an increase of basal extracellular glutamate and postsynaptic structural plasticity in the NAcore. These alterations were strongly related to the CRS-induced reactive microglia and increased TNF-\u03b1 mRNA and protein expression, since by administering minocycline, the impaired glutamate homeostasis and the facilitation of cocaine self-administration were prevented. Our findings are the first to demonstrate that minocycline suppresses the CRS-induced facilitation of cocaine self-administration and glutamate homeostasis disruption in the NAcore. A role of microglia is proposed for the development of glutamatergic mechanisms underpinning stress-induced vulnerability to cocaine addiction."],"dc:format":["application\/vnd.ms-excel"],"dc:language":["eng"],"dc:type":"dataset","dc:rights":["info:eu-repo\/semantics\/restrictedAccess","Datos sujetos al derecho de propiedad intelectual"],"dc:relation":["info:eu-repo\/grantAgreement\/Universidad Nacional de C\u00f3rdoba. Secretaria de Ciencia y Tecnolog\u00eda\/Res., 411\/18","info:eu-repo\/grantAgreement\/Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas\/Res., 411\/18","info:eu-repo\/grantAgreement\/FONDO PARA LA INVESTIGACI\u00d3N CIENT\u00cdFICA Y TECNOL\u00d3GICA\/Res., 411\/18"],"dc:identifier":"https:\/\/repositoriosdigitales.mincyt.gob.ar\/vufind\/Record\/CONICETDig_07fd2e84bafe0dcec7a0a9d9b320335c"}