Disorders of the Nervous System
Author: Marianela Adela Sanchez | Email: marianela.sanchez@unc.edu.ar
Marianela Sanchez 1°, Bethania Mongi – Bragato 1°, Paula Ávalos 1°, Julieta Boezio 1°, Daiana Rigoni 1°, Andrea Guzman 1°, Mariano Bisbal 2°, Flavia Bollati 1°, Liliana Cancela 1°
1° Departamento de Farmacología (IFEC-CONICET) Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, X500HUA, Argentina.
2° Instituto de Investigación Médica Mercedes y Martin Ferreyra (INIMEC – CONICET), Universidad Nacional de Córdoba, X500HUA, Argentina.
Stress is a well-known risk factor in the development of addiction and relapse vulnerability. Studies from our lab, showed that stress can elicit a sensitized response to the psychomotor and stimulant effects of cocaine, as well as a facilitation of cocaine self-administration behavior. Consistently, stress induced alterations in glutamate mechanisms in the nucleus accumbens core (NAcc) have been linked with behavioral findings. Several lines of evidence reported a close linkage between glutamate and the activation of the Nuclear Factor-Kappa B (NF-kB). We propose a central role of Nf-kB signaling in stress -enhanced vulnerability to cocaine self-administration. Thus we designed lentiviral vectors DnIKK, that expresses the dominant negative of the IKK activity to nullify the transcription factor activity. Animals were exposed to stress 2 hs daily for a week. One week after the last stress session, all animals were treated whit lentivirus DnIKK. On day 21, animals were assigned to behavioral studies and biochemical test. Ours results demonstrated that the genetic inhibition of NF-kB, was sufficient to prevent stress-induced cross sensitization to cocaine and the facilitation of cocaine self-administration.These result suggest a central role of NF-kB on the long-term neurobiological mechanism induced in the NAcc by stress, promoting the expression of cross-sensitization to cocaine and facilitation of cocaine self-administration behavior.