Exploring the Antidepressant-like Effects of Ketamine and Synaptic Zinc in a Mouse Model of Depression
Date
2021-01-27
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Abstract
Zinc is critical for proper cellular function due to its role in protein synthesis, brain development, and neural transmission. In the brain, zinc is found at glutamatergic synapses in many regions implicated in regulating emotions. Due to its inhibitory action on glutamatergic receptors and involvement in downstream signalling pathways, zinc is thought to be an important factor in depression. Evidence has shown that in animals and humans, zinc deficiency can lead to depressive-like behaviours and zinc on its own provides antidepressant-like effects. Ketamine, a novel and effective antidepressant, also exerts inhibitory action on the same receptor as zinc and produces rapid and sustained antidepressant effects in both animals and humans. Due to their comparable effects, we aimed to see how zinc and ketamine are involved in depression pathways when examined together. Zinc is transported into synaptic vesicles by zinc transporter 3 (ZnT3). Therefore, to understand the action of synaptic zinc, we used ZnT3 KO mice, mice that lack synaptic zinc, to explore the antidepressant effects of zinc and ketamine in the brain. We compared data found in these mice to ZnT3 HT mice, mice that have approximately half the amount of zinc, and ZnT3 WT mice. The first experiment in this thesis was designed to assess the effects of ketamine treatment on synaptic zinc levels in mood-related structures. No changes in synaptic zinc levels were observed 24h or 7 days after ketamine injection, however sex differences were seen 3 days after ketamine injection. No evidence was found that ketamine causes increases in synaptic zinc levels across all mood-related brain structures. The second experiment aimed to understand the ability of ketamine to reduce depressive-like symptoms in ZnT3 animals subjected to chronic mild stress (CMS), a method of modeling depressive-like symptoms in animals. Overall, CMS was unable to induce depressive-like symptoms in mice and therefore ketamine only had a significant effect in one behavioural test. Animals subjected to stress displayed stress resilience in some tests. ZnT3 KO mice also showed greater resilience to stress than WT mice in some behavioural tests.
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Keywords
Behavioural Neuroscience, Ketamine, Mouse Model, Depression, Zinc
Citation
Markovina, M. (2021). Exploring the Antidepressant-like Effects of Ketamine and Synaptic Zinc in a Mouse Model of Depression (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.