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

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

Montreal

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

International Society of Neurochemistry (ISN) and the American Society of Neurochemistry (ASN)

Comorbidity between stress and cocaine: Role of cofilin in nucleus accumbens during the acquisition of cocaine self-administration.The development of addictive behavior is associated with functional and structural plasticity in the mesocorticolimbic pathway. Animal models have demonstrated that exposure to stress predisposes 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 has shown that repeated stress alters the capacity of a subsequent cocaine injection to modulate dendritic spine morphology and actin dynamics. These findings demonstrate that the pharmacological inhibition of actin polymerization in the nucleus accumbens (NA) prevents stress cross-sensitization with cocaine and influences actin cytoskeleton remodeling in the NA. Thus, the main goal of this project is to evaluate the impact of the actin cytoskeleton in the changes underling the facilitatory influence of stress in the acquisition of cocaine self-administration (SA). 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 SA. Thus, Sprague dawley 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 SA sessions began. Our results reveal that the inhibition of cofilin prevents the stress-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.This work was supported by grants from ISN, CONICET, SECYT and FONCYT.