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CORTICOSTERONE TREATMENT PROVIDES PROTECTION INTO ADULTHOOD FROM THE ADVERSE EFFECTS OF ADOLESCENT SOCIAL DEFEAT

Latsko, Maeson Shea
http://rave.ohiolink.edu/etdc/view?acc_num=kent153251170904353

Abstract Details

2018, PHD, Kent State University, College of Arts and Sciences / Department of Psychological Sciences.
Adolescent social stress can severely impact appropriate adult social behavior, stress responsiveness, and may lead to greater risk of stress-related disorders later in life. We are assessing adolescent stress responses by utilizing a mouse model in which periadolescent (P30) male mice are subjected to repeated aggressive social encounters, followed by tests for social interaction 24 hours (P32) and 30 days (P62) after the last social defeat. When periadolescent mice are tested 24 hours after social defeat, defeated mice interact similar to non-defeated controls, suggesting a negligible immediate effect of social defeat. However, when the same mice are tested again in adulthood, some display social avoidance, whereas others display normal social interaction comparable to non-defeated controls. We have previously reported that increased endogenous glucocorticoid (corticosterone) secretion is correlated with normal social behavior in adulthood following periadolescent social defeat. Here, we assess the effects of corticosterone administration during periadolescence on adult social interaction. Administering corticosterone in drinking water promotes normal adult social behavior, ameliorating the deficits caused by social defeat. Additionally, an intraperitoneal injection of corticosterone at the start of the dark phase of the light:dark cycle (11:30 circadian time, CT) promotes normal social interaction in adulthood, suggesting that glucocorticoid administration might be most effective during the natural circadian peak of corticosterone. Furthermore, administrating a glucocorticoid receptor antagonist eliminates the normalizing effects of corticosterone treatment on adult social behavior, suggesting that corticosterone acts through glucocorticoid receptors. Currently, however we are unable to rule out the possibility that corticosterone may act through mineralocorticoid receptors as well. Decreasing endogenous corticosterone using metyrapone (a corticosterone synthesis inhibitor) does not decrease adult social interaction more than defeat alone, suggesting that low corticosterone is not a risk factor for social avoidance. We also examined mRNA expression changes within the hippocampus, prefrontal cortex, and amygdala in response to social defeat and corticosterone treatment. These experiments reveal important differences in the regulation of gene transcripts by glucocorticoids and GR complexes in adulthood within these brain regions. In particular, cytokines such as tumor necrosis factor and interleukin 1 antagonist differentially regulated following adolescent social defeat. However, corticosterone administration seems to normalize these genes. Given these data, varying corticosterone levels during adolescence may function to offset the prolonged genomic changes associated with adolescent social defeat. These data reveal novel and enduring positive effects of corticosterone administration on adult social behavior following periadolescent social defeat. Translationally, glucocorticoid administration is used to alleviate the effects of trauma in humans. The present data suggest that glucocorticoids could provide long-term benefits in the face of adolescent trauma.
Aaron Jasnow (Advisor)
159 p.
Behavioral Sciences; Neurosciences
Adolescent stress; social defeat; adolescent social defeat; neuroendocrinology; corticosterone

Recommended Citations

Citations

  • Latsko, M. S. (2018). CORTICOSTERONE TREATMENT PROVIDES PROTECTION INTO ADULTHOOD FROM THE ADVERSE EFFECTS OF ADOLESCENT SOCIAL DEFEAT [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent153251170904353

    APA Style (7th edition)

  • Latsko, Maeson. CORTICOSTERONE TREATMENT PROVIDES PROTECTION INTO ADULTHOOD FROM THE ADVERSE EFFECTS OF ADOLESCENT SOCIAL DEFEAT . 2018. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent153251170904353.

    MLA Style (8th edition)

  • Latsko, Maeson. "CORTICOSTERONE TREATMENT PROVIDES PROTECTION INTO ADULTHOOD FROM THE ADVERSE EFFECTS OF ADOLESCENT SOCIAL DEFEAT ." Doctoral dissertation, Kent State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=kent153251170904353

    Chicago Manual of Style (17th edition)

kent153251170904353
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This open access ETD is published by Kent State University and OhioLINK.