Prenatal cannabis exposure impacts on VTA dopamine neuron physiology and adolescent stress susceptibility

Peterson, Colleen Sara

Prenatal cannabis exposure impacts on VTA dopamine neuron physiology and adolescent stress susceptibility

dc.contributor.advisor	Borgland, Stephanie
dc.contributor.author	Peterson, Colleen Sara
dc.contributor.committeemember	Hill, Matthew
dc.contributor.committeemember	Kurrasch, Deborah
dc.contributor.committeemember	Howland, John
dc.contributor.committeemember	Sargin, Derya
dc.date.accessioned	2024-07-05T18:43:06Z
dc.date.available	2024-07-05T18:43:06Z
dc.date.issued	2024-07-03
dc.description.abstract	Cannabis is the third most consumed drug in pregnancy, after alcohol and nicotine. As attitudes around cannabis have changed, overall use has increased, including among pregnant people. The psychoactive constituent of cannabis, Δ9-tetrahydrocannabinol (THC) is lipophilic and can cross the placenta to enter the fetal brain and interact with the endocannabinoid system to effect neurodevelopment. While studies have found that prenatal cannabis exposure increases opioid-seeking and alters the development of mesolimbic dopamine circuitry, its effects on other drugs and other behaviours controlled by the mesolimbic dopamine circuitry, are less understood. In chapter 2, we validate validated acute cannabis intoxication in C57Bl/6 mice with whole cannabis oil made for human consumption, using cannabis tetrad behaviours, and measuring the plasma, brain, and adipose levels of THC and its metabolites. We show that a 5 mg/kg THC dose from whole cannabis oil produces the relevant behaviours and plasma THC levels similar to human consumption of a single 15 mg dose. In chapter 3, we modeled prenatal and early postnatal cannabis exposure (PPCE) in mice, allowing dams access to 5 mg/kg THC from whole cannabis oil in peanut butter from GD1 – PD10, and measured changes in reward circuitry in the offspring. The mesolimbic dopamine circuit consists of dopamine neurons in the ventral tegmental area (VTA) which release dopamine into the nucleus accumbens (NAcc). We found PPCE affected male offspring in particular: VTA dopamine neurons were disinhibited and had increased tonic firing. However, this did not produce alterations to cocaine-seeking behaviour in a conditioned place preference task. In chapter 4, we studied how PPCE affects susceptibility to chronic mild unpredictable stress (CMUS) in adolescence. Tests of anxiety-, anhedonia-, and depression-like, as well as risky behaviours, revealed that PPCE plus CMUS increased risk-taking behaviour in a wire beam bridge task, where fasted animals must cross an unstable bridge to receive food. This thesis provides data on oral exposure to whole cannabis oil, as opposed to pure THC extract, both acutely in adults, across pregnancy, and in offspring. These results broaden our understanding of the effects of PPCE on VTA dopamine neurons, stress, and their associated behaviours.
dc.identifier.citation	Peterson, C. S. (2024). Prenatal cannabis exposure impacts on VTA dopamine neuron physiology and adolescent stress susceptibility (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.uri	https://hdl.handle.net/1880/119126
dc.identifier.uri	https://doi.org/10.11575/PRISM/46722
dc.language.iso	en
dc.publisher.faculty	Graduate Studies
dc.publisher.institution	University of Calgary
dc.rights	University 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.subject	cannabis
dc.subject	prenatal cannabis exposure
dc.subject	chronic stress
dc.subject	adolescent stress
dc.subject	cannabis tetrad
dc.subject	risk-taking
dc.subject	cocaine
dc.subject	VTA
dc.subject	reward
dc.subject	maternal-fetal transfer
dc.subject	oral cannabis
dc.subject.classification	Neuroscience
dc.subject.classification	Pharmacology
dc.title	Prenatal cannabis exposure impacts on VTA dopamine neuron physiology and adolescent stress susceptibility
dc.type	doctoral thesis
thesis.degree.discipline	Medicine – Neuroscience
thesis.degree.grantor	University of Calgary
thesis.degree.name	Doctor of Philosophy (PhD)
ucalgary.thesis.accesssetbystudent	I do not require a thesis withhold – my thesis will have open access and can be viewed and downloaded publicly as soon as possible.