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A new study has uncovered a surprising player in ketamine’s rapid antidepressant effects: astrocytes, the star-shaped support cells of the brain. By studying larval zebrafish, researchers found that ketamine reduces behavioral passivity by altering astrocytic activity in response to futile conditions. Their findings have been published in the journal Neuron .
Ketamine is a medication traditionally used as an anesthetic, but in recent years, it has gained attention for its rapid and long-lasting antidepressant effects at low doses. Unlike conventional antidepressants, which often take weeks to produce noticeable results, ketamine can alleviate symptoms of depression within hours.
This fast-acting property makes it especially promising for conditions like treatment-resistant depression. However, the exact mechanisms behind ketamine’s antidepressant effects remain only partially understood, particularly its influence on non-neuronal brain cells such as astrocytes.
Researchers were interested in larval zebrafish as a model for studying ketamine because of the fish’s unique biological characteristics. Zebrafish are small, transparent, and genetically modifiable, allowing scientists to observe brain-wide activity in real-time.
“We were originally studying a behavior in which larval zebrafish ‘gave up’ in response to their actions becoming futile and thought that this behavior had some similarities to rodent assays (e.g., forced swim task or tail suspension task) commonly used to test antidepressants,” said study author Alex B. Chen, a neuroscience graduate student at Harvard University and graduate research fellow at the Howard Hughes Medical Institute Janelia Research Campus.
“Because the larval zebrafish has unique advantages—it is transparent and small enough that the activity of all of its brain’s neurons can be simultaneously recorded during behavior—we sought to determine whether we could use it to investigate ketamine’s behavioral effects.”
The researchers used larval zebrafish aged 5 to 8 days post-fertilization. These fish were genetically modified to express calcium indicators in neurons or astrocytes, allowing researchers to monitor their activity during experiments. They also employed optogenetic and chemogenetic tools to manipulate specific brain regions and cell types, further investigating the mechanisms underlying observed behavioral changes.
The researchers exposed zebrafish to a transient dose of the drug (200 micrograms per milliliter). The […]
Ketamine’s rapid antidepressant effects traced to overlooked brain cells
