Administering Ketamine to Rickrolled Mice Lacking Vesicular Zinc

Le, Linda Thu

Administering Ketamine to Rickrolled Mice Lacking Vesicular Zinc

dc.contributor.advisor	Dyck, Richard H.
dc.contributor.author	Le, Linda Thu
dc.contributor.committeemember	Antle, Michael C.
dc.contributor.committeemember	Sargin, Derya
dc.contributor.committeemember	Teskey, G. Campbell
dc.date	2023-11
dc.date.accessioned	2023-10-02T16:27:07Z
dc.date.available	2023-10-02T16:27:07Z
dc.date.issued	2023-09-22
dc.description.abstract	Depression is a highly prevalent mood disorder, especially during adolescence and early adulthood. It is commonly treated with antidepressants; however, one-third of patients with depression do not respond to current therapies. Interestingly, it has been found that depression severity is correlated with zinc deficiency, and zinc supplements can improve individuals’ depressive symptoms, potentially through its actions as a neurotransmitter. This phenomenon is facilitated by zinc transporter 3 (ZnT3), which packages zinc into synaptic vesicles. Using a ZnT3 knockout (KO) mouse model that lacks vesicular zinc, we sought to investigate the interplay between vesicular zinc and chronic stress, as well as ketamine, a novel therapeutic for treatment-resistant depression, which has been shown to display rapid and sustained antidepressant-like effects. Wildtype (WT) and ZnT3 KO mice were subjected to multiple simultaneous acute stress (MAS) or kept under standard housing conditions during late adolescence, and subsequently administered ketamine (10 mg/kg) or 0.9% saline. The lack of vesicular zinc in ZnT3 KO mice differentially altered the effects of MAS in behaviours related to anxiety, motivation/apathy, and passive coping, but not anhedonia, in a sex-dependent manner. These data suggest that vesicular zinc modulates stress response. Vesicular zinc, however, did not impact the effects of MAS on neuronal morphology. Moreover, we found limited effects of ketamine in depressive-like behaviours and neuronal structure, but intriguingly, ketamine appeared to compensate for the lack of vesicular zinc in ZnT3 KO mice. Collectively, these findings support that chronic stress impacts behaviour differently in WT and ZnT3 KO mice. However, the single subanaesthetic dose of ketamine administered was not sufficient to alter responses to stress. Further inquiry is warranted to elucidate the combined effect of vesicular zinc and ketamine in stress response.
dc.identifier.citation	Le, L. T. (2023). Administering ketamine to Rickrolled mice lacking vesicular zinc (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.uri	https://hdl.handle.net/1880/117281
dc.identifier.uri	https://doi.org/10.11575/PRISM/42123
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	zinc
dc.subject	ZnT3
dc.subject	chronic stress
dc.subject	ketamine
dc.subject	depression
dc.subject	adolescence
dc.subject.classification	Neuroscience
dc.subject.classification	Psychology--Experimental
dc.title	Administering Ketamine to Rickrolled Mice Lacking Vesicular Zinc
dc.type	master thesis
thesis.degree.discipline	Psychology
thesis.degree.grantor	University of Calgary
thesis.degree.name	Master of Science (MSc)
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.