How Ketamine restores balance - It targets specific receptors (NMDA receptors

Ketamine has been shown to play a significant role in restoring balance in the brain's chemistry, particularly through its interactions with specific receptors such as NMDA receptors. Research supports the idea that ketamine can reverse deficits in dopamine-dependent synaptic plasticity, thereby restoring mood balance in conditions like depression (Belujon & Grace, 2014). By activating D1 receptors and restoring synaptic plasticity in key brain pathways, such as the hippocampus-accumbens pathway, ketamine can help rebalance neurotransmitter activity associated with mood regulation (Belujon & Grace, 2014).

By activating D1 receptors and restoring synaptic plasticity in key brain pathways, such as the hippocampus-accumbens pathway, ketamine can help rebalance neurotransmitter activity associated with mood regulation (Belujon & Grace, 2014).

Introduction

Moreover, studies have indicated that ketamine exerts metaplastic effects on glutamate receptor expression in brain regions like the medial prefrontal cortex and hippocampus, contributing to the reversal of depressive symptoms in individuals resistant to standard therapies (Piva et al., 2021). This suggests that ketamine's ability to modulate glutamatergic activity plays a crucial role in restoring balance in neuronal function associated with mood disorders.

Furthermore, the antidepressant actions of ketamine have been linked to its modulation of NMDA receptors and subsequent effects on neuronal plasticity and synaptic transmission (Zanos & Gould, 2018). By preventing the phosphorylation of certain proteins and activating specific signaling pathways, ketamine can restore balance in neurotransmitter systems affected by mood disorders (Zanos & Gould, 2018).

The research highlights that ketamine's ability to restore balance in the brain's chemistry is closely tied to its interactions with NMDA receptors, modulation of synaptic plasticity, and restoration of neurotransmitter activity in regions crucial for mood regulation. By targeting specific receptors and pathways, ketamine shows promise in rebalancing neuronal function and addressing mood disorders.

References

Belujon, P. and Grace, A. (2014). Restoring mood balance in depression: ketamine reverses deficit in dopamine-dependent synaptic plasticity. Biological Psychiatry, 76(12), 927-936. https://doi.org/10.1016/j.biopsych.2014.04.014

Burrows, M., Kotoula, V., Dipasquale, O., Stringaris, A., & Mehta, M. (2023). Ketamine-induced changes in resting state connectivity, 2 h after the drug administration in patients with remitted depression. Journal of Psychopharmacology, 37(8), 784-794. https://doi.org/10.1177/02698811231189432

Holtzheimer, P., Gao, S., Kirwin, D., & Price, R. (2019). Leveraging neuroplasticity to enhance adaptive learning: the potential for synergistic somatic-behavioral treatment combinations to improve clinical outcomes in depression. Biological Psychiatry, 85(6), 454-465. https://doi.org/10.1016/j.biopsych.2018.09.004

Höflich, A., Kraus, C., Pfeiffer, R., Seiger, R., Rujescu, D., Zarate, C., … & Winkler, D. (2021). Translating the immediate effects of s-ketamine using hippocampal subfield analysis in healthy subjects-results of a randomized controlled trial. Translational Psychiatry, 11(1). https://doi.org/10.1038/s41398-021-01318-6

Kang, M., Hawken, E., & Vázquez, G. (2022). The mechanisms behind rapid antidepressant effects of ketamine: a systematic review with a focus on molecular neuroplasticity. Frontiers in Psychiatry, 13. https://doi.org/10.3389/fpsyt.2022.860882

Kopelman, J., Keller, T., Panny, B., Griffo, A., Degutis, M., Spotts, C., … & Price, R. (2023). Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression. Translational Psychiatry, 13(1). https://doi.org/10.1038/s41398-023-02451-0

Muscat, S., Hartelius, G., Crouch, C., & Morin, K. (2022). Optimized clinical strategies for treatment-resistant depression: integrating ketamine protocols with trauma- and attachment-informed psychotherapy. Psych, 4(1), 119-141. https://doi.org/10.3390/psych4010012

Piva, A., Caffino, L., Mottarlini, F., Pintori, N., Dı́az, F., Fumagalli, F., … & Chiamulera, C. (2021). Metaplastic effects of ketamine and mk-801 on glutamate receptors expression in rat medial prefrontal cortex and hippocampus. Molecular Neurobiology. https://doi.org/10.1007/s12035-021-02352-7

Taraku, B., Woods, R., Boucher, M., Espinoza, R., Jog, M., Al‐Sharif, N., … & Zavaliangos‐Petropulu, A. (2023). Changes in white matter microstructure following serial ketamine infusions in treatment-resistant depression. Human Brain Mapping, 44(6), 2395-2406. https://doi.org/10.1002/hbm.26217

Wilkowska, A. and Cubała, W. (2022). The downstaging concept in treatment-resistant depression: spotlight on ketamine. International Journal of Molecular Sciences, 23(23), 14605. https://doi.org/10.3390/ijms232314605

Zanos, P. and Gould, T. (2018). Mechanisms of ketamine action as an antidepressant. Molecular Psychiatry, 23(4), 801-811. https://doi.org/10.1038/mp.2017.255