{"id":{"repo_id":"unsw","oai_identifier":"oai:unsworks.library.unsw.edu.au:1959.4/101045"},"canonical_url":"https://search.dev.ndltd.org/etd/unsw/oai:unsworks.library.unsw.edu.au:1959.4/101045","repository":{"repo_id":"unsw","name":"University of New South Wales","base_url":"https://unsworks.unsw.edu.au/oai/provider"},"display":{"title":"The long-term effects of reproductive experience on the neurobiology of anxiety and its treatment: a cross species approach in female rats and women","abstract":"This thesis investigated the impact of two female-specific experiences – the reproductive (estrous/menstrual) cycle and reproductive experience (pregnancy/maternal interactions) – on anxiety and its treatment. Following a literature review in Chapter 1, Chapters 2-3 examined whether reproductive experience alters the influence of estrous cycle on anxiety-like behaviour and anxiolytic drug responsivity in rats. Chapter 2 showed that the estrous cycle impacted anxiety-like behaviour and fear extinction (learned fear inhibition) in nulliparous (virgin) rats, but not primiparous (reproductively experienced) rats. Primiparous rats also had altered anxiety-related gene expression (GABAA receptor subunits and corticotrophin-releasing hormone) in the basolateral amygdala and ventral hippocampus. Chapter 3 showed that the estrous cycle impacted diazepam (a benzodiazepine) sensitivity in nulliparous rats, but not primiparous rats. Chapter 4 compared the effects of chronic fluoxetine (an SSRI, the first-line pharmacological treatment for anxiety disorders) in nulliparous versus primiparous rats. Fluoxetine produced anxiogenic-like effects in nulliparous rats, but not primiparous rats; in contrast, fluoxetine reduced stress-induced corticosterone levels in primiparous rats, but not nulliparous rats. Chapters 5-6 investigated candidate mechanisms that may underlie the long-term changes in anxiety and the response to anti-anxiety medications following reproductive experience in adult rats observed in preceding chapters. Chapter 5 showed that pregnancy, rather than maternal experience in the postpartum period, may be necessary to cause estrous-independent anxiety-like behaviour and fear extinction. Chapter 6 found that, compared to nulliparous rats, primiparous rats had a lower peak and blunted decline in circulating allopregnanolone (an anxiolytic neurosteroid implicated in cyclic changes in anxiety and benzodiazepine sensitivity) levels across the estrous cycle. Finally, Chapter 7 translated the rat findings of Chapter 2 to humans by showing that self-reported anxiety and mood symptoms fluctuated over the menstrual cycle in nulliparous human women but not parous human women. Overall, this thesis provided evidence that reproductive experience alters key hormonal, neurobiological, and behavioural features of anxiety and its pharmacological treatment in female rats and women. Potential clinical implications of these findings are discussed.","abstract_html":"This thesis investigated the impact of two female-specific experiences – the reproductive (estrous/menstrual) cycle and reproductive experience (pregnancy/maternal interactions) – on anxiety and its treatment. Following a literature review in Chapter 1, Chapters 2-3 examined whether reproductive experience alters the influence of estrous cycle on anxiety-like behaviour and anxiolytic drug responsivity in rats. Chapter 2 showed that the estrous cycle impacted anxiety-like behaviour and fear extinction (learned fear inhibition) in nulliparous (virgin) rats, but not primiparous (reproductively experienced) rats. Primiparous rats also had altered anxiety-related gene expression (GABAA receptor subunits and corticotrophin-releasing hormone) in the basolateral amygdala and ventral hippocampus. Chapter 3 showed that the estrous cycle impacted diazepam (a benzodiazepine) sensitivity in nulliparous rats, but not primiparous rats. Chapter 4 compared the effects of chronic fluoxetine (an SSRI, the first-line pharmacological treatment for anxiety disorders) in nulliparous versus primiparous rats. Fluoxetine produced anxiogenic-like effects in nulliparous rats, but not primiparous rats; in contrast, fluoxetine reduced stress-induced corticosterone levels in primiparous rats, but not nulliparous rats. Chapters 5-6 investigated candidate mechanisms that may underlie the long-term changes in anxiety and the response to anti-anxiety medications following reproductive experience in adult rats observed in preceding chapters. Chapter 5 showed that pregnancy, rather than maternal experience in the postpartum period, may be necessary to cause estrous-independent anxiety-like behaviour and fear extinction. Chapter 6 found that, compared to nulliparous rats, primiparous rats had a lower peak and blunted decline in circulating allopregnanolone (an anxiolytic neurosteroid implicated in cyclic changes in anxiety and benzodiazepine sensitivity) levels across the estrous cycle. Finally, Chapter 7 translated the rat findings of Chapter 2 to humans by showing that self-reported anxiety and mood symptoms fluctuated over the menstrual cycle in nulliparous human women but not parous human women. Overall, this thesis provided evidence that reproductive experience alters key hormonal, neurobiological, and behavioural features of anxiety and its pharmacological treatment in female rats and women. Potential clinical implications of these findings are discussed.","abstract_has_math":false,"creators":["Pestana, Jodie ; https://orcid.org/0000-0002-2374-9685"],"institution":"UNSW, Sydney","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2023,"date_issued":"2023","date_published":"2023","updated_at":"2026-07-24T05:32:53Z","subjects":["anxiety","menstrual cycle","fear extinction","motherhood","sex hormones","selective serotonin reuptake inhibitor","estrous cycle","anzsrc-for: 520202 Behavioural neuroscience"],"languages":["en"],"rights":["open access","CC BY 4.0","free_to_read"],"rights_urls":["https://purl.org/coar/access_right/c_abf2","https://creativecommons.org/licenses/by/4.0/"],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://doi.org/10.26190/unsworks/24752"],"render_values":[{"text":"https://doi.org/10.26190/unsworks/24752","href":"https://doi.org/10.26190/unsworks/24752","code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/1959.4/101045","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Pestana, Jodie ; https://orcid.org/0000-0002-2374-9685"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2023"]},{"key":"dc:publisher","label":"Institution","values":["UNSW, Sydney"]},{"key":"dc:type","label":"Dc Type","values":["doctoral thesis","http://purl.org/coar/resource_type/c_db06"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["anxiety","menstrual cycle","fear extinction","motherhood","sex hormones","selective serotonin reuptake inhibitor","estrous cycle","anzsrc-for: 520202 Behavioural neuroscience"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["open access","https://purl.org/coar/access_right/c_abf2","CC BY 4.0","https://creativecommons.org/licenses/by/4.0/","free_to_read"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/1959.4/101045","https://unsworks.unsw.edu.au/bitstreams/f2aa76fd-0439-481e-a043-e07f754a3689/download","https://doi.org/10.26190/unsworks/24752"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["This thesis investigated the impact of two female-specific experiences – the reproductive (estrous/menstrual) cycle and reproductive experience (pregnancy/maternal interactions) – on anxiety and its treatment. Following a literature review in Chapter 1, Chapters 2-3 examined whether reproductive experience alters the influence of estrous cycle on anxiety-like behaviour and anxiolytic drug responsivity in rats. Chapter 2 showed that the estrous cycle impacted anxiety-like behaviour and fear extinction (learned fear inhibition) in nulliparous (virgin) rats, but not primiparous (reproductively experienced) rats. Primiparous rats also had altered anxiety-related gene expression (GABAA receptor subunits and corticotrophin-releasing hormone) in the basolateral amygdala and ventral hippocampus. Chapter 3 showed that the estrous cycle impacted diazepam (a benzodiazepine) sensitivity in nulliparous rats, but not primiparous rats. Chapter 4 compared the effects of chronic fluoxetine (an SSRI, the first-line pharmacological treatment for anxiety disorders) in nulliparous versus primiparous rats. Fluoxetine produced anxiogenic-like effects in nulliparous rats, but not primiparous rats; in contrast, fluoxetine reduced stress-induced corticosterone levels in primiparous rats, but not nulliparous rats. Chapters 5-6 investigated candidate mechanisms that may underlie the long-term changes in anxiety and the response to anti-anxiety medications following reproductive experience in adult rats observed in preceding chapters. Chapter 5 showed that pregnancy, rather than maternal experience in the postpartum period, may be necessary to cause estrous-independent anxiety-like behaviour and fear extinction. Chapter 6 found that, compared to nulliparous rats, primiparous rats had a lower peak and blunted decline in circulating allopregnanolone (an anxiolytic neurosteroid implicated in cyclic changes in anxiety and benzodiazepine sensitivity) levels across the estrous cycle. Finally, Chapter 7 translated the rat findings of Chapter 2 to humans by showing that self-reported anxiety and mood symptoms fluctuated over the menstrual cycle in nulliparous human women but not parous human women. Overall, this thesis provided evidence that reproductive experience alters key hormonal, neurobiological, and behavioural features of anxiety and its pharmacological treatment in female rats and women. Potential clinical implications of these findings are discussed."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["The long-term effects of reproductive experience on the neurobiology of anxiety and its treatment: a cross species approach in female rats and women"]}]}],"canonical_facts":{"dc:creator":["Pestana, Jodie ; https://orcid.org/0000-0002-2374-9685"],"dc:date":["2023"],"dc:description":["This thesis investigated the impact of two female-specific experiences – the reproductive (estrous/menstrual) cycle and reproductive experience (pregnancy/maternal interactions) – on anxiety and its treatment. Following a literature review in Chapter 1, Chapters 2-3 examined whether reproductive experience alters the influence of estrous cycle on anxiety-like behaviour and anxiolytic drug responsivity in rats. Chapter 2 showed that the estrous cycle impacted anxiety-like behaviour and fear extinction (learned fear inhibition) in nulliparous (virgin) rats, but not primiparous (reproductively experienced) rats. Primiparous rats also had altered anxiety-related gene expression (GABAA receptor subunits and corticotrophin-releasing hormone) in the basolateral amygdala and ventral hippocampus. Chapter 3 showed that the estrous cycle impacted diazepam (a benzodiazepine) sensitivity in nulliparous rats, but not primiparous rats. Chapter 4 compared the effects of chronic fluoxetine (an SSRI, the first-line pharmacological treatment for anxiety disorders) in nulliparous versus primiparous rats. Fluoxetine produced anxiogenic-like effects in nulliparous rats, but not primiparous rats; in contrast, fluoxetine reduced stress-induced corticosterone levels in primiparous rats, but not nulliparous rats. Chapters 5-6 investigated candidate mechanisms that may underlie the long-term changes in anxiety and the response to anti-anxiety medications following reproductive experience in adult rats observed in preceding chapters. Chapter 5 showed that pregnancy, rather than maternal experience in the postpartum period, may be necessary to cause estrous-independent anxiety-like behaviour and fear extinction. Chapter 6 found that, compared to nulliparous rats, primiparous rats had a lower peak and blunted decline in circulating allopregnanolone (an anxiolytic neurosteroid implicated in cyclic changes in anxiety and benzodiazepine sensitivity) levels across the estrous cycle. Finally, Chapter 7 translated the rat findings of Chapter 2 to humans by showing that self-reported anxiety and mood symptoms fluctuated over the menstrual cycle in nulliparous human women but not parous human women. Overall, this thesis provided evidence that reproductive experience alters key hormonal, neurobiological, and behavioural features of anxiety and its pharmacological treatment in female rats and women. Potential clinical implications of these findings are discussed."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/1959.4/101045","https://unsworks.unsw.edu.au/bitstreams/f2aa76fd-0439-481e-a043-e07f754a3689/download","https://doi.org/10.26190/unsworks/24752"],"dc:language":["en"],"dc:publisher":["UNSW, Sydney"],"dc:rights":["open access","https://purl.org/coar/access_right/c_abf2","CC BY 4.0","https://creativecommons.org/licenses/by/4.0/","free_to_read"],"dc:subject":["anxiety","menstrual cycle","fear extinction","motherhood","sex hormones","selective serotonin reuptake inhibitor","estrous cycle","anzsrc-for: 520202 Behavioural neuroscience"],"dc:title":["The long-term effects of reproductive experience on the neurobiology of anxiety and its treatment: a cross species approach in female rats and women"],"dc:type":["doctoral thesis","http://purl.org/coar/resource_type/c_db06"]},"updated_at":"2026-07-24T05:32:53Z"}