Approximately 20% of people experience at least one depressive episode during their lifetime. Furthermore, a majority of these individuals do not experience full remission of symptoms following current treatment protocols. Drug development has been slow, as the etiology of mood disorders is multifactorial and poorly understood; individual susceptibility is influenced by complex gene-environment interactions. Stress is often reported to precede or exacerbate depressive illness, and is therefore used to model depressive-like symptomatology in laboratory animals. While existing paradigms have been useful, few take into account the cumulative effects of genetics and/or experiences that underlie stress-sensitivity. Naturalistic paradigms that utilize multiple risk factors may better model the development of affective disorders.
These studies examined the effects of prenatal stress on the hypothalamic-pituitary-adrenal (HPA) axis, central serotonergic markers and social status of male rats. As adults, prenatal stress was not associated with altered basal corticosterone (CORT) or CORT response to acute restraint. However, fewer serotonergic neurons were observed within specific subregions of the dorsal raphé nucleus (DRN) of prenatally stressed males. The number of c-Fos immunoreactive serotonergic neurons did not differ in response to acute restraint, suggesting similar levels of activation, and therefore similar CORT response. However, the overall reduction in the number of serotonergic neurons suggests that the potential for differential activation exists. We hypothesized that a different type of challenge in adulthood, like chronic stress, may reveal differences in serotonergic and HPA activity.
As adults, males were housed in the visible burrow system (VBS), a unique housing system designed to reflect the natural environment of rats. The VBS utilizes social stress, which is ethologically relevant to rats and has clear translational value to humans. Chronic social stress, in particular, is associated with the development of mood disorders, and the phenotype of socially subordinate male rats shares many similarities with human depressive symptomatology.
These studies were performed to determine if prenatal stress, a putative risk factor, would increase the likelihood of social subordination. We hypothesized that adult prenatally stressed males would be more susceptible to subordination, and that the combination of prenatal and subordination stress would augment depressive-like symptoms observed in subordinate males. As adults, 2 males, (1 prenatally stressed and 1 non-prenatally stressed male) were housed with 4 females in each VBS. Consistent with our prediction, prenatal stress biased social status; these males became subordinate in 75% of burrows. However, there was no exacerbation of subordinate phenotype in these males; rather, they appeared better adapted to subordinate status. They lost less weight, engaged in fewer agonistic interactions and had fewer wounds than subordinate males in prior studies. Prenatally stressed subordinates also had lower basal CORT than non-prenatally stressed subordinates at the end of VBS housing.
These findings are consistent with the stress match/mismatch hypothesis; adverse prenatal environment may prepare offspring for adversity in adulthood. The mechanisms underlying this effect are unclear, but the observed reduction of serotonergic neurons in the DRN suggests serotonin-mediated alterations in coping strategy. Future studies should address this possibility.
","abstract_html":"<p>Approximately 20% of people experience at least one depressive episode during their lifetime. Furthermore, a majority of these individuals do not experience full remission of symptoms following current treatment protocols. Drug development has been slow, as the etiology of mood disorders is multifactorial and poorly understood; individual susceptibility is influenced by complex gene-environment interactions. Stress is often reported to precede or exacerbate depressive illness, and is therefore used to model depressive-like symptomatology in laboratory animals. While existing paradigms have been useful, few take into account the cumulative effects of genetics and/or experiences that underlie stress-sensitivity. Naturalistic paradigms that utilize multiple risk factors may better model the development of affective disorders. </p><p>These studies examined the effects of prenatal stress on the hypothalamic-pituitary-adrenal (HPA) axis, central serotonergic markers and social status of male rats. As adults, prenatal stress was not associated with altered basal corticosterone (CORT) or CORT response to acute restraint. However, fewer serotonergic neurons were observed within specific subregions of the dorsal raphé nucleus (DRN) of prenatally stressed males. The number of c-Fos immunoreactive serotonergic neurons did not differ in response to acute restraint, suggesting similar levels of activation, and therefore similar CORT response. However, the overall reduction in the number of serotonergic neurons suggests that the potential for differential activation exists. We hypothesized that a different type of challenge in adulthood, like chronic stress, may reveal differences in serotonergic and HPA activity. </p><p> As adults, males were housed in the visible burrow system (VBS), a unique housing system designed to reflect the natural environment of rats. The VBS utilizes social stress, which is ethologically relevant to rats and has clear translational value to humans. Chronic social stress, in particular, is associated with the development of mood disorders, and the phenotype of socially subordinate male rats shares many similarities with human depressive symptomatology. </p><p>These studies were performed to determine if prenatal stress, a putative risk factor, would increase the likelihood of social subordination. We hypothesized that adult prenatally stressed males would be more susceptible to subordination, and that the combination of prenatal and subordination stress would augment depressive-like symptoms observed in subordinate males. As adults, 2 males, (1 prenatally stressed and 1 non-prenatally stressed male) were housed with 4 females in each VBS. Consistent with our prediction, prenatal stress biased social status; these males became subordinate in 75% of burrows. However, there was no exacerbation of subordinate phenotype in these males; rather, they appeared better adapted to subordinate status. They lost less weight, engaged in fewer agonistic interactions and had fewer wounds than subordinate males in prior studies. Prenatally stressed subordinates also had lower basal CORT than non-prenatally stressed subordinates at the end of VBS housing. </p><p>These findings are consistent with the stress match/mismatch hypothesis; adverse prenatal environment may prepare offspring for adversity in adulthood. The mechanisms underlying this effect are unclear, but the observed reduction of serotonergic neurons in the DRN suggests serotonin-mediated alterations in coping strategy. Future studies should address this possibility.</p>","abstract_has_math":false,"creators":["Scott, Karen A."],"institution":"University of Cincinnati","degree_name":"PhD","degree_level":"doctoral","degree_discipline":"Medicine: Neuroscience/Medical Science Scholars Interdisciplinary","degree_department":null,"school":null,"contributors":["Sakai, Randall"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012","date_published":"2012","updated_at":"2026-07-24T03:36:39Z","subjects":["Neurology","prenatal stress","HPA axis","serotonin","social stress","mood disorders","corticosterone"],"languages":["English"],"rights":["unrestricted","This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://rave.ohiolink.edu/etdc/view?acc_num=ucin1354550657","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Sakai, Randall"]},{"key":"dc:creator","label":"Author","values":["Scott, Karen A."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2012"]},{"key":"dc:publisher","label":"Institution","values":["University of Cincinnati / OhioLINK"]},{"key":"dc:type","label":"Dc Type","values":["Electronic Thesis or Dissertation"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Medicine: Neuroscience/Medical Science Scholars Interdisciplinary"]},{"key":"thesis:degree_level","label":"Degree Level","values":["doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["PhD"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Cincinnati"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Neurology","prenatal stress","HPA axis","serotonin","social stress","mood disorders","corticosterone"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]},{"key":"dc:rights","label":"Dc Rights","values":["unrestricted","This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://rave.ohiolink.edu/etdc/view?acc_num=ucin1354550657"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Approximately 20% of people experience at least one depressive episode during their lifetime. Furthermore, a majority of these individuals do not experience full remission of symptoms following current treatment protocols. Drug development has been slow, as the etiology of mood disorders is multifactorial and poorly understood; individual susceptibility is influenced by complex gene-environment interactions. Stress is often reported to precede or exacerbate depressive illness, and is therefore used to model depressive-like symptomatology in laboratory animals. While existing paradigms have been useful, few take into account the cumulative effects of genetics and/or experiences that underlie stress-sensitivity. Naturalistic paradigms that utilize multiple risk factors may better model the development of affective disorders.
These studies examined the effects of prenatal stress on the hypothalamic-pituitary-adrenal (HPA) axis, central serotonergic markers and social status of male rats. As adults, prenatal stress was not associated with altered basal corticosterone (CORT) or CORT response to acute restraint. However, fewer serotonergic neurons were observed within specific subregions of the dorsal raphé nucleus (DRN) of prenatally stressed males. The number of c-Fos immunoreactive serotonergic neurons did not differ in response to acute restraint, suggesting similar levels of activation, and therefore similar CORT response. However, the overall reduction in the number of serotonergic neurons suggests that the potential for differential activation exists. We hypothesized that a different type of challenge in adulthood, like chronic stress, may reveal differences in serotonergic and HPA activity.
As adults, males were housed in the visible burrow system (VBS), a unique housing system designed to reflect the natural environment of rats. The VBS utilizes social stress, which is ethologically relevant to rats and has clear translational value to humans. Chronic social stress, in particular, is associated with the development of mood disorders, and the phenotype of socially subordinate male rats shares many similarities with human depressive symptomatology.
These studies were performed to determine if prenatal stress, a putative risk factor, would increase the likelihood of social subordination. We hypothesized that adult prenatally stressed males would be more susceptible to subordination, and that the combination of prenatal and subordination stress would augment depressive-like symptoms observed in subordinate males. As adults, 2 males, (1 prenatally stressed and 1 non-prenatally stressed male) were housed with 4 females in each VBS. Consistent with our prediction, prenatal stress biased social status; these males became subordinate in 75% of burrows. However, there was no exacerbation of subordinate phenotype in these males; rather, they appeared better adapted to subordinate status. They lost less weight, engaged in fewer agonistic interactions and had fewer wounds than subordinate males in prior studies. Prenatally stressed subordinates also had lower basal CORT than non-prenatally stressed subordinates at the end of VBS housing.
These findings are consistent with the stress match/mismatch hypothesis; adverse prenatal environment may prepare offspring for adversity in adulthood. The mechanisms underlying this effect are unclear, but the observed reduction of serotonergic neurons in the DRN suggests serotonin-mediated alterations in coping strategy. Future studies should address this possibility.
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These studies examined the effects of prenatal stress on the hypothalamic-pituitary-adrenal (HPA) axis, central serotonergic markers and social status of male rats. As adults, prenatal stress was not associated with altered basal corticosterone (CORT) or CORT response to acute restraint. However, fewer serotonergic neurons were observed within specific subregions of the dorsal raphé nucleus (DRN) of prenatally stressed males. The number of c-Fos immunoreactive serotonergic neurons did not differ in response to acute restraint, suggesting similar levels of activation, and therefore similar CORT response. However, the overall reduction in the number of serotonergic neurons suggests that the potential for differential activation exists. We hypothesized that a different type of challenge in adulthood, like chronic stress, may reveal differences in serotonergic and HPA activity.
As adults, males were housed in the visible burrow system (VBS), a unique housing system designed to reflect the natural environment of rats. The VBS utilizes social stress, which is ethologically relevant to rats and has clear translational value to humans. Chronic social stress, in particular, is associated with the development of mood disorders, and the phenotype of socially subordinate male rats shares many similarities with human depressive symptomatology.
These studies were performed to determine if prenatal stress, a putative risk factor, would increase the likelihood of social subordination. We hypothesized that adult prenatally stressed males would be more susceptible to subordination, and that the combination of prenatal and subordination stress would augment depressive-like symptoms observed in subordinate males. As adults, 2 males, (1 prenatally stressed and 1 non-prenatally stressed male) were housed with 4 females in each VBS. Consistent with our prediction, prenatal stress biased social status; these males became subordinate in 75% of burrows. However, there was no exacerbation of subordinate phenotype in these males; rather, they appeared better adapted to subordinate status. They lost less weight, engaged in fewer agonistic interactions and had fewer wounds than subordinate males in prior studies. Prenatally stressed subordinates also had lower basal CORT than non-prenatally stressed subordinates at the end of VBS housing.
These findings are consistent with the stress match/mismatch hypothesis; adverse prenatal environment may prepare offspring for adversity in adulthood. The mechanisms underlying this effect are unclear, but the observed reduction of serotonergic neurons in the DRN suggests serotonin-mediated alterations in coping strategy. Future studies should address this possibility.
"],"dc:format":["application/pdf","p.158","2.5 MB"],"dc:identifier":["http://rave.ohiolink.edu/etdc/view?acc_num=ucin1354550657"],"dc:language":["English"],"dc:publisher":["University of Cincinnati / OhioLINK"],"dc:rights":["unrestricted","This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws."],"dc:subject":["Neurology","prenatal stress","HPA axis","serotonin","social stress","mood disorders","corticosterone"],"dc:title":["Alterations in adult behavior as a result of early life manipulations"],"dc:type":["Electronic Thesis or Dissertation"],"thesis:degree_discipline":["Medicine: Neuroscience/Medical Science Scholars Interdisciplinary"],"thesis:degree_level":["doctoral"],"thesis:degree_name":["PhD"],"thesis:institution_name":["University of Cincinnati"]},"updated_at":"2026-07-24T03:36:39Z"}