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

RIGONI DAIANA; AVALOS MARIA PAULA; GUZMAN ANDREA SUSANA; BISBAL MARIANO; BOEZIO MARIA JULIETA; CANCELA LILIANA M; BOLLATI FLAVIA

Cordoba

Congreso; 2018 Meeting of Argentine Society for Research in Neuroscience; 2018

Sociedad Argentina de Neurociencias

Animals models have demonstrated that exposure to stresspredisposes to developing substance use disorders.We havepreviously shown that repeated stress alters the capacity ofa subsequent cocaine injection to modulate dendritic spinemorphology and actin dynamics. Our findings indicates thatthe pharmacological inhibition of actin polymerization in thenucleus accumbens (NA) prevents stress cross-sensitizationwith cocaine and influences actin cytoskeleton remodeling inthe NA. Thus, the main goal of this project is to evaluate theimpact of the actin cytoskeleton in the changes underling thefacilitatory influence of cocaine after exposure to chronicstress in the acquisition of cocaine self-administration (SA).For this purpose, we have generated a lentivirus containing ashort hairpin RNA (shRNA) specific to cofilin, to inhibit itsexpression in NA, and explore its function during the acquisitionof cocaine SA. Thus, Sprague Dawley rats pre-exposedto chronic restraint stress will be administered intra-accumbenswith shRNA of cofilin, and later they will undergo surgeryfor implantation of catheters in the jugular vein 1 weekbefore SA sessions. In the same line of evidence, our resultsrevealed that the inhibition of cofilin is sufficient to preventthe expression of cross-sensitization between stress andcocaine, suggesting that the cofilin regulation is crucial inthe facilitatory influence of stress on the vulnerability todevelop cocaine addiction.