“Cross sensitization between stress and cocaine is associated to nuclear factor kappa B (NF-kB) activation in the nucleus accumbens

SANCHEZ MA; MONGI-BRAGATO B; AVALOS MP; GUZMAN AS; RIGONI D; VEDELAGO G; BISBAL M; BOLLATI FA; CANCELA LM

Congreso; XXXVI Congreso anual (virtual) de la Sociedad Argentina de Investigación en Neurociencias.; 2021

Sociedad Argentina de Investigación en Neurociencias.

Stressful experience-induced cocaine-related behaviors were associated with a significantimpairment of glutamatergic mechanisms in the nucleus accumbens core (NAcc). NF-kB, aubiquitous transcription factor, induce the expression of gene targets tightly linked to gliamaintenance of glutamate homeostasis. Here, using a genetic and pharmacologicalstrategy, we evaluate the impact of NF-kB abrogation in NAcc on the long-term expressionof restraint stress-induced behavioral cross-sensitization to cocaine. Thus, we usedlentiviral vectors expressing a dominant negative to the IKK (dn IKK) and the potentpharmacological inhibitor of NF-kB nuclear translocation, PDTC, to nullify the transcription factor activity. Chronically pre-stressed were administered intra-NAcc with dnIKK 7 days, or PDTC 20 minutes before a cocaine challenge administration, respectively. After treatment, behavioral sensitization and NF-kB levels were evaluated. Repeated stressinduced a significant NF-kB activation in the NAcc. Consistently, the pharmacological orgenetic inhibition of NF-kB activation, was sufficient to prevent stress-inducedsensitization to cocaine. These results suggest a central role of NF-kB on the long-termneurobiological mechanism induced by stress in the NAcc, promoting the expression ofcross-sensitization to cocaine. Furthermore, our findings help to understand the neuraland molecular basis of the comorbidity between exposure to stress and cocaine abuse.