Session: 10

PS10-13 | Cross sensitization between stress and cocaine is associated to nuclear factor kappa B (NF-kB) activation in the nucleus accumbens

Marianela Adela Sanchez

Instituto de Farmacología Experimental IFEC - CONICET

Stressful experience-induced cocaine-related behaviors were associated with a significant impairment of glutamatergic mechanisms in the nucleus accumbens core (NAcc). NF-kB, a ubiquitous transcription factor, induce the expression of gene targets tightly linked to glia maintenance of glutamate homeostasis. Here, using a genetic and pharmacological strategy, we evaluate the impact of NF-kB abrogation in NAcc on the long-term expression of restraint stress-induced behavioral cross-sensitization to cocaine. Thus, we used lentiviral vectors expressing a dominant negative to the IKK (dn IKK) and the potent pharmacological 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 stress induced a significant NF-kB activation in the NAcc. Consistently, the pharmacological or genetic inhibition of NF-kB activation, was sufficient to prevent stress-induced sensitization to cocaine. These results suggest a central role of NF-kB on the long-term neurobiological mechanism induced by stress in the NAcc, promoting the expression of cross-sensitization to cocaine. Furthermore, our findings help to understand the neural and molecular basis of the comorbidity between exposure to stress and cocaine abuse.