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

RIGONI D.; AVALOS M. P.; GUZMÁN A. S.; BISBAL MARIANO; CANCELA L.M; BOLLATI F.

Cordoba

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

Sociedad Argentina de Investigacion en Neurociencias

Animals models have demonstrated that exposure to stress predisposes todeveloping substance use disorders.We have previously shown that repeatedstress alters the capacity of a subsequent cocaine injection tomodulatedendritic spine morphology and actin dynamics. Our findings indicatesthat thepharmacologicalinhibition of actin polymerization in the NA prevents stresscross-sensitization with cocaine and influencesactin cytoskeleton remodelingin the nucleus accumbens (NA). Thus, the main goal of this project is toevaluatethe impact of the actin cytoskeleton in the changes underling thefacilitatory influence of cocaine after exposureto chronic stress in theacquisition of cocaine self-administration (SA). For this purpose, we havegenerated alentivirus containing a short hairpin RNA (shRNA) specific tocofilin, to inhibit its expression in NA, and exploreits function during theacquisition of cocaine SA. Thus, Sprague dawley rats pre-exposed to chronicrestraintstress, will be administered intra-accumbens with shRNA of cofilin, andlater they will undergo surgery forimplantationof catheters in the jugular vein one week before SA sessions. In the same line of evidence, ourresults revealedthat the inhibition of cofilin is sufficient to prevent the expression ofcross-sensitization betweenstress and cocaine, suggesting that the cofilin regulationis crucial in the facilitatory influence of stress on thevulnerability todevelop cocaine addiction.