Restricted (Penn State Only)
Caruso, Michael J
Graduate Program:
Biobehavioral Health
Doctor of Philosophy
Document Type:
Date of Defense:
June 13, 2017
Committee Members:
  • Sonia A. Cavigelli, Dissertation Advisor
  • Sonia A. Cavigelli, Committee Chair
  • Helen M. Kamens, Committee Member
  • David J. Vandenbergh, Committee Member
  • Koraly Perez-Edgar, Outside Member
  • Helen M. Kamens, Dissertation Advisor
  • adolescent
  • social stress
  • HPA Axis
  • glucocorticoid
  • nicotine
  • anxiety
  • depression
A variety of stress-related psychopathologies including affective disorders such as anxiety, depression, and nicotine use, emerge during adolescence. Development of comorbid affective disorders and nicotine use has been attributed to hypothalamic-pituitary-adrenal axis (HPA) dysregulation associated with chronic stress during adolescent development. However, few studies have simultaneously investigated adolescent stress effects on affective behavior, HPA activity, and nicotine responses in animal models. Rodent models of chronic social stress are ethologically relevant models that may provide valuable insight into mechanisms that underlie adolescent affective disorders and nicotine use comorbidity. However, the results of these studies are inconsistent as they are highly dependent on individual differences in stress susceptibility. In the current dissertation, I have shown that baseline individual differences in exploratory behavior (i.e. temperament) in outbred rats modulates the impact of adolescent social experience on adult HPA activity (Chapter 2). These findings suggest that temperament is one factor that contributes to inconsistent findings in adolescent stress literature. Additional sources of variability in the literature include genetic variation among outbred rodents and sex differences in stress-susceptibility. For the next study (Chapter 3), I developed a novel adolescent social stress protocol, referred to as chronic variable social stress (CVSS), to control for these potential sources of variability by exposing inbred male and female mice to multiple temperament- and sex-specific stressors. CVSS included repeated cycles of social isolation and housing with novel social partners. We found that adolescent CVSS increased adult anxiety/depression-related behavior and blunted HPA activity. In the last study (Chapter 4), I replicated and extended these previous findings by simultaneously investigating the impact of adolescent CVSS on anxiety/depression-related behavior, HPA activity, and nicotine responses. I found that male inbred (BALB/cJ) mice exposed to adolescent CVSS exhibited reduced exploratory behavior and altered behavioral and physiological responses to nicotine. However, there was little relationship between anxiety/depression-related behavior and nicotine responses within individuals. The studies presented herein may help clarify the factors that contribute to inconsistent findings across rodent adolescent social stress models. Furthermore, identification of the factors that promote maladaptive health trajectories (i.e., development of affective disorders and nicotine use) during adolescence can inform future studies on the biological and environmental determinants of adolescent development.