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dc.contributor.advisorÅgmo, Anders
dc.contributor.authorLe Moëne, Olivia
dc.date.accessioned2019-09-06T08:05:26Z
dc.date.available2019-09-06T08:05:26Z
dc.date.issued2019-06-06
dc.description.abstractA number of psychiatric troubles are distributed along a biased sex ratio. Differences in sex steroids levels, notably estradiol, could account for this bias. Differential expression and activation of the two known estrogen receptors (ER), α and β could result in different behavioral patterns. Indeed, these two receptors play an important, but unequal, role in the regulation of socio-sexual and fear-related behaviors. First, I ethologically characterized anxiety-related behaviors in adult female rats. Then, I systematically administered ER agonists to observe the role of ERs on behavioral responses and structure. Finally, I evaluated the role of the ERs in specific brain areas by silencing the expression of either the ERα or the ERβ with local administration of shRNA encoded with an adeno-associated virus directed against each of these receptors. All studies were conducted in a seminatural environment in order to obtain externally valid, transferable results. In this environment, several emotion-inducing stimuli were introduced to determinate ERs’ involvement on situation-dependent behavioral responses. ERα activation was necessary for the display of lordosis and paracopulatory behaviors in female rats, as well as for their sexual attractivity to males. Expression of ERα in the ventral nucleus of the hypothalamus (VMN) was necessary for lordosis. The receptor in the VMN also showed anxiogenic properties during exposure to white noise. My findings suggest that ERα in the VMN had anxiogenic properties in threatening situations, and facilitated copulation in safe environments. Treatment with ERβ agonist modified behavioral structure during exposure to aversive stimuli, and silencing this receptor in the CeA increased rat anxiety. Therefore, I conclude that ERβ has anxiolytic properties, partly acting through the CeA. Better understanding of the implications of each ER within different brain structures will help unveiling their seemingly opposite roles.en_US
dc.description.doctoraltypeph.d.en_US
dc.description.popularabstractSex is a significant risk factor in psychiatric troubles. The levels of circulating sex hormones could partly explain this. Estradiol, the main female hormone, binds to two receptors, estrogen receptor α (ERα) and estrogen receptor β (ERβ). To unveil the differential role of ERs, I administered ER agonists to female rats in a first experiment. Then, I silenced the expression of either the ERα or the ERβ in the ventromedial nucleus of the hypothalamus (VMN) or the central amygdala (CeA). Female rats were then submitted to a sequence of emotional challenges eliciting positive (lavender odor, chocolate pellets) or negative affects (fox odor, musical, white noise). My findings suggest that ERα in the VMN facilitated copulation in safe environments, and had anxiogenic properties in threatening situations. ERβ had anxiolytic properties, partly acting through the CeA. These actions might not be opposite, but rather result from different information processing by distinct brain structures.en_US
dc.description.sponsorshipFaculty of Health Sciences, University of Tromsøen_US
dc.identifier.urihttps://hdl.handle.net/10037/16106
dc.language.isoengen_US
dc.publisherUiT The Arctic University of Norwayen_US
dc.publisherUiT Norges arktiske universiteten_US
dc.relation.haspart<p>Paper I: Le Moëne, O. & Ågmo, A. (2019). Responses to positive and aversive stimuli in estrous female rats housed in a seminatural environment: Effects of yohimbine and chlordiazepoxide. <i>Pharmacology, Biochemistry and Behavior, 179</i>, 43-54. Also available in Munin at <a href=https://hdl.handle.net/10037/17126>https://hdl.handle.net/10037/17126</a>. <p>Paper II: Le Moëne, O. & Ågmo, A. (2018). Behavioral responses to emotional challenges in female rats living in a seminatural environment: The role of estrogen receptors. <i>Hormones and Behavior, 106</i>, 162-177. Also available at <a href= https://doi.org/10.1016/j.yhbeh.2018.10.013> https://doi.org/10.1016/j.yhbeh.2018.10.013. </a> Submitted manuscript available in Munin at <a href=https://hdl.handle.net/10037/14573> https://hdl.handle.net/10037/14573</a>. <p>Paper III: Le Moëne, O., Stavarache, M., Ogawa, S., Musatov, S. & Ågmo, A. (2019). Estrogen receptors α and β in the central amygdala and the ventromedial nucleus of the hypothalamus: sociosexual behaviors, fear and arousal in female rats during emotionally challenging events. (Accepted manuscript). Published version in <i>Behavioural Brain Research, 367</i>, 128-142, available in Munin at <a href=https://hdl.handle.net/10037/15606>https://hdl.handle.net/10037/15606</a>.en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2019 The Author(s)
dc.subject.courseIDDOKTOR-003
dc.subjectVDP::Medical disciplines: 700::Health sciences: 800::Medical/dental ethics, behavioural sciences, history: 805en_US
dc.subjectVDP::Medisinske Fag: 700::Helsefag: 800::Medisinsk/odontologisk etikk, atferdsfag, historie: 805en_US
dc.subjectVDP::Mathematics and natural science: 400::Zoology and botany: 480::Ethology: 485en_US
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Zoologiske og botaniske fag: 480::Etologi: 485en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Pharmacology: 728en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Farmakologi: 728en_US
dc.titleEstrogenic modulation of socio-sexual and fear-related behaviors in female rats: Properties of the estrogen receptors α and β in a procedure with external validityen_US
dc.typeDoctoral thesisen_US
dc.typeDoktorgradsavhandlingen_US


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