Ketamine for a Boost of Neural Plasticity: How, but Also When?

Summary & key facts

Researchers looked at how a single dose of ketamine makes brain cells more able to form new connections. In mouse brains and brain slices they found a short window of time, a few hours after the drug, when neurons were much more likely to grow new tiny branches that help neurons talk to each other. That boost needed dopamine acting through a specific receptor and a follow-on cell signal. The effect on this readiness to change faded within about 12 hours, while the longer-lasting increase in the number of actual connections showed up later. These results help explain how ketamine can act fast against depression, but the work was done in mice and brain tissue, so it does not prove the same timing or exact steps happen in people.

Key facts:

• In mouse brain slices, a single dose of ketamine raised the chance that a neuron would form a new connection from about one in five times to about one in two times within a few hours after treatment.
• The increase in neurons’ readiness to form new connections showed up around 2 to 4 hours after ketamine and was gone by about 12 hours, while a lasting rise in the total number of connections appeared later, within a day or more.
• The plasticity boost required dopamine acting at a specific receptor called Drd1. Blocking that receptor or stopping dopamine release prevented ketamine’s effect on new connections.
• Activating the same dopamine receptor directly mimicked ketamine’s ability to increase the chance of making new connections, and the cell signal called protein kinase A was needed downstream of that receptor.
• In a mouse model of stress-related, depressive-like behavior, ketamine protected both the brain’s ability to form new connections and the animals’ motivated behavior. Stimulating dopamine release in the frontal cortex also rescued behavior, while shutting down dopamine there blocked ketamine’s benefit.
• These experiments were done in mice and in slices of mouse brain. That means the exact timing and molecular steps might differ in people, and other brain mechanisms besides dopamine are likely involved.

Topics

Neuroscience and Neuropharmacology Research Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Antidepressant Cognition Dendritic spine Depression (economics) Dopamine Dopaminergic Economics Hippocampal formation Hippocampus Ketamine Macroeconomics Neuroplasticity Neuroscience Prefrontal cortex Psychology

Substances

Ketamine

Conditions & symptoms

Depression Lack of energy or motivation Sadness or low mood