title: Development and Validation of an Animal Model of Gestational Cannabis Exposure: Prenatal and Postnatal Outcomes
Creators: name: Baglot, Samantha Lorraine
Publisher: name: Graduate Studies
Year: 2024
Subjects: subject: Cannabis
subject: Prenatal Cannabis Exposure
subject: Pharmacokinetics
subject: Animal Model
subject: Development
subject: THC
subject: Pregnancy
subject: Rat
subject: Inhalation
subject: Vapour
subject: Translational
subject: Anxiety-like Behaviour
subject: Neuroimmune
subject: Stress Response
subject: Metabolism
subject: Feeding Behaviour
subject: Stress-Reactive Behaviour
subject: Social Behaviour
subject: Adiposity
subject: Maternal-fetal transmission
subject: Endocannabinoid
subject: Neuroscience
subject: Psychology--Developmental
subject: Psychology--Behavioral
subject: Psychology--Physiological
subject: Psychology--Experimental
subject: Pharmacology
subject: Immunology
subject: FOS: Clinical medicine
subject: Mental Health

description: Cannabis 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.