Impact of stress in the vulnerability to cocaine addiction: Role of cofilin during the acquisition of cocaine self-administration in nucleus accumbens.

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

Buenos Aires

Congreso; 2nd Federation of Latin-American and Caribbean Societies for Neuroscience (FALAN).; 2016

Preclinical studies using the model of self-administration (AA) support the idea of a proactive influence of stress. Studies from our laboratory revealed that repeated stress alters the capacity of a subsequent cocaine injection to modulate dendritic spine morphology, actin dynamics and AMPAR expression in the nucleus accumbens (NA) core. We have demonstrated that the pharmacological inhibition of actin polymerization in the NA prevents stress cross-sensitization with cocaine. 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. 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 self- administration. Thus, Sprague Dolly rats were exposed to chronic restraint stress two hours daily during 7 days. Stressed and control animals were administered with an intra-accumbens injection of lentiviral particles the next day after the final stress (day 8). One week after the intracranial injection all animals were anaesthetized for surgery for implantation of permanents catheters in the right jugular vein and 7 days later self-administration sessions began. Our preliminary data suggests that the inhibition of cofilin prevents the acquisition of cocaine self-administration in animals pre-exposed to chronic stress.