S-088 | Stress-induced vulnerability to cocaine addiction is linked to Nuclear Factor Kappa B (NF-κB) activation in the Nucleus Accumbens Core

Disorders of the Nervous System
Author: Bethania Mongi-Bragato | Email: bethania.mongi@unc.edu.ar

Bethania Mongi- Bragato^1°, Marianela Sánchez^1°, Boezio Julieta^1°,  Avalos Maria Paula^1°, Bisbal Mariano^2°, Eduardo Perassi^3°, Flavia Bollati^1°,  Liliana Cancela^1°

^1° Instituto de Farmacología Experimental de Córdoba (IFEC-CONICET) – Departamento de Farmacología Otto Orsingher, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba
^2° Instituto de Investigación Médica Mercedes y Martin Ferreyra (INIMEC – CONICET)
^3° Instituto de Investigaciones en Físico-Química de Córdoba, INFIQC-CONICET, Departamento de Química Teórica y Computacional, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba

Stress-induced cocaine-related behaviors are associated with significant impairment of the glutamate mechanism in the Nucleus Accumbens core (NAcore). The hallmark of impaired glutamate homeostasis following stress is the downregulation of the glutamate transporter (GLT-1). Several evidences have reported a strong link between GLT-1 and the Nuclear factor-kappa B (NF-kB), which controls genes targets for glial glutamate regulation. The present study evaluated the involvement of NF-kB signaling in stress-induced vulnerability to cocaine addiction. We used lentiviral vectors DNIKK which expresses a dominant negative of IKK activity, to knock down transcription factor activity. Pre-stressed animals received DNIKK intra-NAcore one week after the last stress session. On day 21, animals were assigned to immunohistochemical, biochemical, or behavioral studies. Stress induces a marked activation of NF-kB pathway in the NAcore. Consistently, inhibition of NF-kB activation could reverse the facilitatory effect of stress on the acquisition of cocaine self-administration. Furthermore, DNKK administration prevented stress-induced GLT-1 downregulation in the NAcore. Immunofluorescence analysis in pre-stressed animals revealed a strong expression of NF-kB in astrocytes, the cells where 90% of GLT-1 is expressed. These findings reveal a critical role for NF-kB in the neurobiological mechanisms underlying the comorbidity between stress exposure and addictive disorders