Ketamine therapy has emerged as a promising treatment for mood disorders such as depression and anxiety. Its rapid-acting effects on mood regulation are attributed to its unique brain action mechanism. Although the exact process is not yet fully understood, ketamine is known to act on the glutamatergic system, enhancing synaptic plasticity and promoting neurogenesis.
Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist. This means it blocks the activity of the NMDA receptor, a type of glutamate receptor that plays a critical role in learning, memory, and synaptic plasticity (1). By blocking NMDA receptors, ketamine triggers a cascade of events leading to the release of brain-derived neurotrophic factor (BDNF), a protein that supports the growth and survival of neurons (2). This increase in BDNF levels enhances synaptic plasticity and neurogenesis, promoting the formation of new neural connections and potentially improving mood regulation (3).
Furthermore, ketamine’s action on the NMDA receptors leads to a rapid increase in glutamate levels, the brain’s primary excitatory neurotransmitter (4). This glutamate surge stimulates the activation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors, which have been implicated in the rapid antidepressant effects of ketamine (5).
It is important to note that ketamine therapy for mood disorders is typically administered at sub-anesthetic doses, significantly lower than the doses used for anesthesia or recreational purposes. This ensures that the treatment is both safe and effective.
In conclusion, ketamine therapy is believed to alter mood regulation by blocking NMDA receptors, increasing BDNF levels, and stimulating AMPA receptors, promoting neuroplasticity and potentially alleviating depressive symptoms.
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