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

SANCHEZ M. A.; AVALOS M. P.; EULIARTE P. V.; , GUZMÁN A. S.; , RIGONI D.; BOLLATI F.; CANCELA LILIANA M

Cordoba

Congreso; XXXIII Congreso de la sociedad Argentina de la investigacion en neurociencia; 2018

Sociedad Argentina de investigación en Neurociencia

Scientific background has shown stress-induced long-lasting neuroadaptations on glutamatergic innervations to Nucleus Accumbens (NA) in animal models. Our previews studies revealed chronic restraint stress-induced increase in basal glutamate (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 of GLU 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 of microglia activation, suggesting the participation of these cells in the studied phenomenon. In the present project, we propose the increase of TNFα and activation of NF-kB as key contributors of the stress-induced dysregulation of GLU homeostasis, post-synaptic changes and cocaine SA. Thus, rats will be administrated with lentiviral vectors targeted TNFα or NF-kB in NA core and a cocaine SA model will 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 morphology of dendritic spines. In this way, we put forward the use of gene manipulation techniques in order to deepen the study of the underlying neurobiological basis of the comorbidity between stress exposure and cocaine abuse.