Impact of stress in the vulnerability to cocaine addiction: role of cofilin in nucleus accumbens

RIGONI D; AVALOS, M.P.; GUZMAN A; BISBAL M; BOEZIO JULIETA; CANCELA LM.; BOLLATI, FLAVIA A.

Cordoba

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

Sociedad Argentina de Investigación en Neurociencia

Animal models have demonstrated that exposure to stress predisposes to developing substance use disorders. We have previously shown that repeated stress alters the capacity of a subsequent cocaine injection to modulate dendritic spine morphology and actin dynamics. Our findings indicatesthat the pharmacological inhibition of actin polymerization in the NA prevents stress cross-sensitization with cocaine and influences actin cytoskeleton remodeling in the nucleus accumbens (NA).Thus, the main goal of this project is to evaluate the impact of the actin cytoskeleton in the changes underling the facilitatory influence of cocaine after exposure to chronic stress in the acquisition of cocaine self-administration (SA). For this purpose, we have generated a lentivirus containing a short hairpin RNA (shRNA) specific to cofilin, to inhibit its expression in NA, and explore its function during the acquisition of cocaine SA. Thus, Sprague dawley rats pre-exposed to chronic restraint stress,will be administered intra-accumbenswith shRNA of cofilin,and later they will undergo surgery for implantation of catheters in the jugular vein one week before SA sessions. In the same line of evidence, our results revealed that the inhibition of cofilin is sufficient to prevent the expression of cross-sensitization between stress and cocaine, suggesting that the cofilinregulation is crucial in the facilitatory influence of stress on the vulnerability to develop cocaine addiction.