Volume 36, Issue. 6, June, 2020

Social Isolation in Male Rats During Adolescence Inhibits the Wnt/b-Catenin Pathway in the Prefrontal Cortex and Enhances Anxiety and Cocaine-Induced Plasticity in Adulthood

Santiago Cuesta 1,2,3 • Alejandrina Funes 1,2 • Alejandra M. Pacchioni 1,2

1 A´ rea Toxicologı´a, Departamento de Ciencias de los Alimentos y del Medioambiente, Facultad de Ciencias Bioquı´micas y Farmace´uticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Santa Fe, Argentina

2 Consejo Nacional de Investigaciones Cientı´ficas y Te´cnicas, Rosario, Argentina

3 Present Address: Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA


In adult animals, it is well established that stress has a proactive effect on psychostimulant responses. However, whether only a short period of stress during adolescence can also affect cocaine responses later in life and what mechanisms are involved are unknown. Here, we showed that 5 days of social isolation during rat adolescence had a long-term impact on anxiety-like behaviors, cocaine-induced conditioned place preference, and the expression of sensitization during adulthood. At the molecular level, social isolation decreased the activity of the Wnt/b-catenin pathway in the prefrontal cortex (PFC). Furthermore, after the expression of cocaine sensitization, isolated rats showed an increase in this pathway in the nucleus accumbens. Together, these findings suggest that, adolescent social isolation by altering the Wnt/b-catenin pathway in the developing PFC might increase the cocaine responses during adulthood, introducing this pathway as a novel neuroadaptation in the cortical-accumbens connection that may mediate a stress-induced increase in vulnerability to drugs.


Social isolation; Adolescence; Cocaine vulnerability; Wnt/b-catenin pathway


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