Disorders of the Nervous System
Author: Maria Paula Avalos | email: mp.avalos@unc.edu.ar
Maria Paula Avalos 1°, Andrea Susana Guzman 1°, Bethania Mongi-Bragato 1°, Marianela Adela Sanchez 1°, Georgina Vedelago 1°, Gastón Diego Calfa 1°, Flavia Andrea Bollati 1°, Liliana Marina Cancela 1°
1° Instituto de Farmacología Experimental de Córdoba (IFEC-CONICET), Departamento de Farmacología Otto Orsingher, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Though the facilitating influence of stress on drug abuse is well documented, the mechanisms underlying this interaction have yet to be fully elucidated. The present study explores the glutamatergic mechanisms in the nucleus accumbens core (NAcore) underpinning the sensitized response to the psychomotor-stimulating effects of cocaine following chronic restraint stress (CRS). Adult male Wistar rats were restrained for 2 hours/day for seven days (day 1-7). From day 17 until completing the experimental protocol (day 17-21), animals received a 5-day systemic treatment with ceftriaxone, a known enhancer of the glutamate transporter GLT-1, or vehicle. On day 21, all animals were randomly assigned to behavioral, microscopic, biochemical or neurochemical tests. Our results demonstrated that ceftriaxone prevents the increase of basal extracellular glutamate concentrations and changes in structural plasticity in the NAcore of CRS-experienced animals. These alterations were thought to underlie CRS-induced behavioral cross-sensitization to cocaine, since by restoring glutamate transport in the NAcore with ceftriaxone, the facilitating influence of stress on the sensitized response to the psychomotor-stimulating effects of cocaine was blocked. These results emphasize the biological importance of GLT-1 in the NAcore as a vulnerability marker in the comorbidity between stress and substance use disorders.