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Antidepressants' cellular target

Nature volume 486, page 9 (07 June 2012) | Download Citation

Certain antidepressant drugs seem to work by acting on a tiny population of brain cells in the cortex. Identifying the specific cells targeted by these drugs, which are known as serotonin-specific reuptake inhibitors (SSRIs), could aid the development of more selective medicines.

Nathaniel Heintz and his team at the Rockefeller University in New York homed in on a group of cortical neurons that express a protein called p11 — levels of which are decreased in depression. This protein regulates the signalling of the transmitter serotonin in the brain.

Mice that were treated long-term with the SSRI fluoxetine showed alterations in the expression of many genes in p11-producing cortical neurons, but not in neurons that lacked p11. When the researchers deleted the gene that encodes p11 from cortical neurons, the mice no longer responded to the SSRI in behavioural tests that model aspects of depression.

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