Role of cofilin in nucleus accumbens core during the crosssensitization between chronic stress and cocaine

RIGONI D; AVALOS MP; BISBAL M; GUZMAN S; CANCELA LM; BOLLATI F

Mar del Plata

Congreso; XXX Reunion Anual De La Sociedad Argentina De Investigacion En Neurociencias; 2015

Sociedad Argentina de Investigación en Neurociencias - SAN -

Several evidences support the idea of a proactive influence of stress on drug-addiction.Studies from our laboratory revealed that repeated stress alters the capacity of asubsequent cocaine injection to modulate dendritic spine morphology, actin dynamics andAMPAR expression in the nucleus accumbens (NA) core. We have demonstrated that theinhibition of actin polymerization in the NA prevents stress cross-sensitization withcocaine. Thus, the main goal of this project is to evaluate the impact of the actincytoskeleton in the changes underling the facilitatory influence of cocaine after chronicstress. 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 duringcross-sensitization between stress and cocaine. Thus, Wistar rats will be exposed to chronicrestraint stress two hours daily during 7 days. Stressed and control animals will beadministered with an intra-accumbens injection of lentiviral vector 20 days (day 8) before achallenge with cocaine administered 3 weeks after the final stress (day 28), whenbehavioral sensitisation to cocaine was evaluated. Our preliminary data suggests that theinhibition of cofilin is sufficient to prevent the expression of cross-sensitization betweenstress and cocaine. Future studies will attempt to identify the upstream signaling pathwaysregulating cofilin activity during stress induced cross sensitization to cocaine.