Cellular and Molecular Neurobiology
Author: María Julieta Boezio | email: jboezio@unc.edu.ar
M. Julieta Boezio 1°, Daiana Rigoni 1°, Milena Jandar Paz 2°, Mariano Bisbal 2°, Liliana Cancela 1°, Agustín Anastasía 2°, Flavia Bollati 1°
1° Instituto de Farmacología Experimental de Córdoba (IFEC-CONICET), Departamento de Farmacología Otto Orsingher, FCQ-UNC-Córdoba, Argentina
2° Instituto de Investigación Médica Mercedes y Martin Ferreyra, INIMEC-CONICET, Córdoba, Argentina
Brain-derived neurotrophic factor (BDNF) is a neurotrophin widely expressed in the brain that plays a major role in the development, differentiation, maturation and plasticity of the nervous system. BDNF has a fundamental role in neuronal plasticity leading to drug abuse. In the last decades, a single nucleotide polymorphism in the BDNF gene, resulting in the substitution of the amino acid Valine for Methionine in codon 66 (Val66Met) in the BDNF prodomain region, has been widely associated with stress disorders and drug abuse. The aim of this study is evaluate the involvement of Met-prodomain of BDNF (Met-pBDNF) in the impact of stress-induced vulnerability to cocaine addiction. For this purpose, we generated lentiviral (LV) particles expressing the prodomain, pBDNF Met and pBDNF Val. Male rats were randomly assigned to the NS (not stress) and S (stress) groups and underwent stereotaxic surgery to bilaterally microinject LV particls of pBDNF variants in the nucleus accumbens core (NAc). After a cocaine challenge, we observed an increase in locomotor activity in stressed Met-pBDNF animals. In correlation with these changes, we also observed a lasting decrease in GLT-1 levels in NAc. This result is relevant since it is considered one of the mechanisms underlying the vulnerability to develop addictive behaviors induced by stress. Our results suggest that Met-pBDNF is involved in stress-induced vulnerability to cocaine addiction, acquiring additional value as an active ligand.