Carlos Novoa 1, Thomas J. Gould 1 1 Department of Biobehavioral Health

Adolescence is a sensitive developmental window characterized by profound changes in brain circuitry, amplifying both adaptability and vulnerability to environmental influences. Social stress during this period is a prominent risk factor for adverse psychiatric outcomes later in life. This study investigates the interplay between adolescent social stress and genetic background in determining anxiety-related behaviors and nicotine sensitivity. Using male C57BL/6J and C57BL/6NJ mice, we assessed the physiological and behavioral impacts of adolescent social instability stress (SIS). Our results demonstrate that adolescent SIS significantly impairs body weight gain throughout late adolescence. Regarding behavioral indicators, SIS increases spontaneous locomotion and anxiety-like behaviors in the elevated plus maze. Furthermore, physiological assessments revealed that SIS induces the accumulation of hair corticosterone (CORT) while the HPA response to an acute pharmacological challenge with nicotine was attenuated. Adolescent stress altered subsequent nicotine sensitivity, resulting in a reduced recovery from acute nicotine hypolocomotor effects. Finally, genetic background significantly influenced baseline behavior and drug reactivity, with distinct straindependent differences observed in both anxiety and locomotor activity. These findings underscore the critical role of genetic factors in shaping individual vulnerability to mental health challenges and substance use following adolescent stress.

The Pennsylvania State University