Comorbidity between chronic restraint stress and cocaine self-administration: role of glial proteins in nucleus accumbens plasticity

SANCHEZ, M.; AVALOS, M.P.; GUZMÁN, ANDREA S.; EULIARTE P.V.; RIGONI D; BOLLATI, FLAVIA A.; CANCELA LM.

Cordoba

Congreso; XXXIII Congress of the Argentine Society for Research in Neuroscience; 2018

Sociedad Argentina de Investigación en Neurociencia

Scientific background has shown stress-induced long-lasting neuroadaptations onglutamatergic innervations to Nucleus Accumbens (NA) in animal models. Ourpreviews studies revealed chronic restraint stress-induced increase in basalglutamate (GLU) levels- and decrease in GLU transporter, GLT-1, levels in NA core.These results have been suggested as a hallmark of the homeostatic disruption ofGLU transmission and have been associated with the facilitation of cocaine selfadministration (SA) induced by stress. In parallel, our data showed chronic stressinduced enhancement of TNF-α mRNA levels in NA core after a cocaine challenge.Moreover, all these alterations were prevented by minocycline, a potent inhibitor ofmicroglia activation, suggesting the participation of these cells in the studiedphenomenon. In the present project, we propose the increase of TNFα andactivation of NF-kB as key contributors of the stress-induced dysregulation of GLUhomeostasis, post-synaptic changes and cocaine SA. Thus, rats will be administratedwith lentiviral vectors targeted TNFα or NF-kB in NA core and a cocaine SA modelwill be used to evaluate: 1)Glial modulation of TNFα/NF-kB on GLU homeostasis,2)GLT-1 levels, 3)currents mediated by AMPA and NMDA receptors and morphologyof dendritic spines. In this way, we put forward the use of gene manipulationtechniques in order to deepen the study of the underlying neurobiological basis ofthe comorbidity between stress exposure and cocaine abuse.