The active role of Met prodomain in cocaine sensitization induced by chronic stress

BOEZIO MJ; RIGONI D; JANDAR PAZ M; VACCARO V; BISBAL M; CANCELA LM; ANASTASIA A; BOLATTI F

Buenos Aires

Congreso; XXXVII Congreso anual de la Sociedad Argentina de Investigación en Neurociencias.; 2022

Sociedad Argentina de Investigación en Neurociencias.

Brain-derived neurotrophic factor (BDNF) is aneurotrophin widely expressed in the brain that plays a major role in thedevelopment, differentiation, maturation and plasticity of the nervous system.BDNF has a fundamental role in neuronal plasticity leading to drug abuse. In thelast decades, a single nucleotide polymorphism in the BDNF gene, resulting inthe substitution of the amino acid Valine for Methionine in codon 66 (Val66Met)in the BDNF prodomain region, has been widely associated with stress disordersand drug abuse. The aim of this study is evaluate the involvement ofMet-prodomain of BDNF (Met-pBDNF) in the impact of stress-induced vulnerabilityto cocaine addiction. For this purpose, we generated lentiviral (LV) particlesexpressing the prodomain, pBDNF Met and pBDNF Val. Male rats were randomlyassigned to the NS (not stress) and S (stress) groups and underwent stereotaxicsurgery to bilaterally microinject LV particls of pBDNF variants in the nucleusaccumbens core (NAc). After a cocaine challenge, we observed an increase inlocomotor activity in stressed Met-pBDNF animals. In correlation with thesechanges, we also observed a lasting decrease in GLT-1 levels in NAc. Thisresult is relevant since it is considered one of the mechanisms underlying thevulnerability to develop addictive behaviors induced by stress. Our resultssuggest that Met-pBDNF is involved in stress-induced vulnerability to cocaineaddiction, acquiring additional value as an active ligand.