Development and Validation of an Animal Model of Gestational Cannabis Exposure: Prenatal and Postnatal Outcomes

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dc.contributor.advisorHill, Matthew N.
dc.contributor.authorBaglot, Samantha Lorraine
dc.contributor.committeememberKurrasch, Deborah M.
dc.contributor.committeememberBorgland, Stephanie L.
dc.date2024-11
dc.date.accessioned2024-09-17T21:49:17Z
dc.date.available2024-09-17T21:49:17Z
dc.date.issued2024-09-13
dc.description.abstractCannabis is one of the most widely used drugs, even during pregnancy. Clinical and preclinical research have shown important but variable effects of prenatal cannabis exposure (PCE) on cognitive, social, emotional, and metabolic domains. Preclinical studies allow for precise control and mechanistic exploration; however, studies utilizing translational routes of administration (such as inhalation) are limited. The overall aim of this thesis was to validate a preclinical model of cannabis inhalation and then use that model during pregnancy to examine maternal-fetal transmission and both pre- and post-natal outcomes across several domains. In chapter 2, we characterized and validated a preclinical model of cannabis inhalation and compared pharmacokinetics with injection exposure. Despite comparable dosages and similar peak blood THC levels following inhalation and injection, we found drastically different metabolism and pharmacokinetics of THC and metabolites. In chapter 3, we validated a preclinical model of inhaled PCE and compared maternal-fetal transmission to a common PCE injection model. We found that inhalation exposure resulted in a transmission rate (from maternal blood to fetal brain) of about 30%, whereas injection resulted in roughly 100%. These studies were the first to directly compare THC and metabolite levels following inhalation or injection in adulthood and during pregnancy, and taken together our results suggest that animal models need to consider route of administration when discussing translational implications. In chapter 4 and 5, we aimed to examine the effects of inhaled PCE on several pre- and postnatal outcome domains. In general, we found that PCE resulted in altered early-life immune profile, reduced social investigation, elevated stress-response in adult males, altered glucose metabolism that was sex and diet dependent, modified food choice, and reduced sucrose preference in adulthood. However, we also found that PCE did not alter maternal outcomes, litter size or birthweight, embryonic endocannabinoid or stress system functioning, adolescent structural brain development or social play behaviour, and adult anxiety-like behaviour, bodyweight, or adiposity. Collectively, these studies provide a large overview of the effects of PCE utilizing a moderate inhalation dosage and may help promote more accurate public health messaging around the risk of cannabis use during pregnancy.
dc.identifier.citationBaglot, S. L. (2024). Development and validation of an animal model of gestational cannabis exposure: prenatal and postnatal outcomes (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.urihttps://hdl.handle.net/1880/119733
dc.language.isoen
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgary
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectCannabis
dc.subjectPrenatal Cannabis Exposure
dc.subjectPharmacokinetics
dc.subjectAnimal Model
dc.subjectDevelopment
dc.subjectTHC
dc.subjectPregnancy
dc.subjectRat
dc.subjectInhalation
dc.subjectVapour
dc.subjectTranslational
dc.subjectAnxiety-like Behaviour
dc.subjectNeuroimmune
dc.subjectStress Response
dc.subjectMetabolism
dc.subjectFeeding Behaviour
dc.subjectStress-Reactive Behaviour
dc.subjectSocial Behaviour
dc.subjectAdiposity
dc.subjectMaternal-fetal transmission
dc.subjectEndocannabinoid
dc.subject.classificationNeuroscience
dc.subject.classificationPsychology--Developmental
dc.subject.classificationPsychology--Behavioral
dc.subject.classificationPsychology--Physiological
dc.subject.classificationPsychology--Experimental
dc.subject.classificationPharmacology
dc.subject.classificationImmunology
dc.subject.classificationMental Health
dc.titleDevelopment and Validation of an Animal Model of Gestational Cannabis Exposure: Prenatal and Postnatal Outcomes
dc.typedoctoral thesis
thesis.degree.disciplineMedicine – Neuroscience
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.thesis.accesssetbystudentI do not require a thesis withhold – my thesis will have open access and can be viewed and downloaded publicly as soon as possible.
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