Signaling pathways underlying the rapid antidepressant actions of ketamine

Summary & key facts

Researchers reviewed how a low dose of ketamine can lift depressive symptoms very quickly. In people, ketamine can start helping within hours and a single dose can keep helping for about a week. In rodents, the drug rapidly rebuilt tiny connections between brain cells in the prefrontal cortex and boosted the proteins that make those connections work. Those changes happened after the drug was gone and may explain the fast effects. The work points to new drug targets, but most of the detailed brain findings come from animal studies and more research is needed on safety and how long the brain changes last.

Key facts:

• Typical antidepressant medicines often take weeks to work, and only about one in three people respond to the first medicine they try.
• Clinical studies showed that a low dose of ketamine can produce antidepressant effects within hours and the benefit can last for roughly a week after a single dose.
• Right after a low dose, people sometimes have mild dissociative or psychosis-like effects starting in about half an hour that usually wear off by about an hour.
• In rodents, a single low dose of ketamine quickly increased the number of mature dendritic spines, which are the tiny contact points where brain cells connect, in the prefrontal cortex.
• Those new spines were linked to stronger electrical signals between neurons, showing the connections were more functional, not just more numerous.
• Ketamine reversed the loss of spines and the weak brain signals caused by weeks of chronic stress in animal models, and it reversed stress-linked depression-like behaviors in those models.
• The drug activated a protein pathway called mTOR, which helps cells make proteins, and this was followed by higher levels of synaptic proteins that support new connections.
• Because most of the detailed signaling and spine data come from animal studies, we do not yet know exactly how long the new connections last in people or whether other drugs can safely copy ketamine’s effects.

Topics

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

Categories

Health Sciences Medicine Pharmacology

Tags

Antidepressant Cognition Hippocampus Internal medicine Ketamine Medicine Milnacipran Neuroscience NMDA receptor Prefrontal cortex Psychology Receptor Synapse Synaptogenesis

Substances

Ketamine

Conditions & symptoms

Depression Lack of energy or motivation Sadness or low mood