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

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

Buenos Aires

Congreso; 2nd FALAN Congress; 2016

FALAN

Preclinical studies using the model of self-administration (AA) support the idea of a proactive influenceof stress. Studies from our laboratory revealed that repeated stress alters the capacity of a subsequentcocaine injection to modulate dendritic spine morphology, actin dynamics and AMPAR expression in thenucleus accumbens (NA) core. We have demonstrated that the pharmacological inhibition of actinpolymerization in the NA prevents stress cross-sensitization with cocaine. Thus, the main goal of thisproject is to evaluate the impact of the actin cytoskeleton in the changes underling the facilitatoryinfluence of cocaine after exposure to chronic stress in the acquisition of cocaine self-administration. Forthis purpose we have generated a lentivirus containing a short hairpin RNA (shRNA) specific to cofilin, toinhibit its expression in NA, and explore its function during the acquisition of cocaine selfadministration. Thus, Sprague Dolly rats were exposed to chronic restraint stress two hours daily during7 days. Stressed and control animals were administered with an intra-accumbens injection of lentiviralparticles the next day after the final stress (day 8). One week after the intracranial injection all animalswere anaesthetized for surgery for implantation of permanents catheters in the right jugular vein and 7days later self-administration sessions began. Our preliminary data suggests that the inhibition of cofilinprevents the acquisition of cocaine self-administration in animals pre-exposed to chronic stress.