Administering Ketamine to Rickrolled Mice Lacking Vesicular Zinc
Date
2023-09-22
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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.
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Keywords
zinc, ZnT3, chronic stress, ketamine, depression, adolescence
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.