Comorbidity between stress and cocaine: Role of cofilin in nucleus accumbens during the acquisition of cocaine self-administration

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

Congreso; International Society of Neurochemistry (ISN) and the American Society of Neurochemistry (ASN); 2019

The development of addictive behavior is associated with functional and structural plasticity inthe mesocorticolimbic pathway. Animal models have demonstrated that exposure to stresspredisposes to developing substance use disorders. This ability to inducing persistent restructuring of neuronal cell in the limbic regions of brain is thought to be responsible for long-term behavioral plasticity driving addiction. Our laboratory hasshown that repeated stress alters the capacity of a subsequent cocaine injection to modulate dendritic spine morphology and actindynamics. These findings demonstrate that the pharmacological inhibition of actinpolymerization in the nucleus accumbens (NA) prevents stress cross-sensitization with cocaineand influences actin cytoskeleton remodeling in the NA. Thus, the main goal of this project is toevaluate the impact of the actin cytoskeleton in the changes underling the facilitatory influenceof stress in the acquisition of cocaine self-administration (SA). For this purpose, we havegenerated a lentivirus containing a short hairpin RNA (shRNA) specific to cofilin, to inhibit itsexpression in NA, and explore its function during the acquisition of cocaine SA. Thus, Spraguedawley rats were exposed to chronic restraint stress two hours daily during 7 days. Stressed andcontrol animals were administered with an intra-accumbens injection of lentiviral particles thenext day after the final stress (day 8). One week after the intracranial injection all animals wereanaesthetized for surgery for implantation of permanents catheters in the right jugular vein and7 days later SA sessions began. Our results reveal that the inhibition of cofilin prevents thestress-induced sensitization to cocaine and reverts the facilitation of the acquisition of cocaine self-administration induced by stress, suggesting that cofilin regulation is crucial for the stress-induced facilitation on the vulnerability to develop cocaine addiction.