Neurochemistry and Neuropharmacology
Author: Maria Julieta Boezio | Email: jboezio@unc.edu.ar
M. Julieta Boezio1°, Daiana Rigoni1°, Marianela Sanchez1°, Bethania Mongi-Bragato1°, Victoria Vaccaro, Liliana Cancela1°, Mariano Bisbal2°, Agustin Anastasia2°, Flavia Bollati
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)
Stress is a significant risk factor in the development of addiction and relapse vulnerability. Research from our lab has shown that stress heightens the psychomotor and stimulant effects of cocaine and facilitates the acquisition of cocaine self-administration behavior. The reasons behind some individuals’ greater risk for substance use disorders remain unclear, but these differences might be explained by genetic variants. The Val66Met variant of brain-derived neurotrophic factor (BDNF), which impairs BDNF transport and activity-dependent secretion, has been associated with increased susceptibility to neuropsychiatric and substance use disorders, due to its role in nervous system development and plasticity. In this study, we evaluate the Met prodomain BDNF (Met-pBDNF) in stress-related vulnerability to cocaine addiction. For this purpose, we generated lentiviral (LV) particles carrying Met-pBDNF and Val-pBDNF variants and microinjected them into the nucleus accumbens core (NAc). Our results show increased locomotor activity and facilitated cocaine self-administration in stressed Met-pBDNF rats compared to stressed and non-stressed Val-pBDNF animals. Moreover, we observed increased AMPAR surface expression in stressed Met-pBDNF rats, consistent with our previous findings. These results suggest a novel and crucial role for Met-pBDNF in the neurobiological mechanisms underlying the comorbidity between stress exposure and addiction disorders.