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

AVALOS, M.P.; ESPARZA MA; GARCIA KELLER C; VIRGOLINI M; CANCELA LM.

Cordoba

Congreso; XXVIII CONGRESO ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACION EN NEUROCIENCIAS; 2013

Sociedad Argentina de Investigación en Neurociencias

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