Stress and vulnerability to develop cocaine addiction: role of glial proteins in nucleus accumbens plasticity

AVALOS, M.P.; ESPARZA A; CONSTANZA GARCIA KELLER; MIRIAM B. VIRGOLINI; CANCELA L

Huerta Grande, Cordoba

Congreso; XXVIII Congreso SAN 2013; 2013

Sociedad Argentina de investigación en Neurociencia

In this project we will use a cocaine self-administration (SA) model to determinate the behavioral interactions between chronic stress and cocaine, and neurobiological mechanisms associated to the neuropathology of cocaine abuse in cortical glutamatergic projections to basal ganglia. The restraint stress was implicated in the proactive influence of rewarding and stimulating properties of a non-contingent administration of amphetamine and cocaine (Esparza et al, 2012; Garcia-Keller et al, 2013). In this model we will evaluate: 1) influence of glial modulation (GLT-1) on the glutamate (Glu) homeostasis, 2) morphology of dendritic spines of nucleus accumbens (NAc) core and shell, 3) effect of ceftriaxone and minocycline (drugs that inhibit the glial activation and also affect GLT-1 levels). Our approach is that deregulation of glutamate homeostasis by stress and cocaine self-administration consist of a marked increase of Glu in core (extrasynaptic and synaptic), consistent with a decrease of GLT-1 glial protein and changes in density and morphology of dendritic spines in NAc core. Thus, we expect to determinate neurobiological mechanisms to demonstrate rationally how stress promotes substances consume. At the same time, pharmacological studies will allow us to evaluate drugs effects which are based upon the restoration of glial homeostasis and thereby repair the plasticity of glutamatergic synapses and the changes induced by stress or drugs in cocaine self-administration.