Mechanism of Prozac mood-boost unlocked
In a move that could hold the key to better drugs to beat a range of mood disorders including depression, French scientists have solved a vital piece of the puzzle of how certain antidepressants work.
For over 50 years it's been known that too little of the nerve transmitter serotonin in the brain is linked to low mood, while drugs like Prozac that raise the levels of the agent have a mood-boosting effect. But it's remained a mystery why, despite measurable responses to the drug occurring almost immediately after it's given, depression sufferers still need to take the drug for more than three weeks before they begin to feel better.
Now, writing in Science, Paris-Descartes University scientist Anne Baudry and her colleagues have discovered the delay is down to the time the brain takes to turn one type of nerve cell into another, which in turn leads to symptomatic improvements. Using both cultured cells and experimental mice, the team found that administering Prozac (fluoxetine) turns on the production in the cell of a small molecule known as micro RNA 16 (miR-16) which, in turn, stops cells from producing uptake pumps that deactivate serotonin.
However, unexpectedly, they also found that the Prozac molecule triggers a different family of neurones, which normally use the nerve transmitter chemical noradrenaline, to turn off their production of miR-16. This causes the cells to turn on genes that pick up and recycle "spare" serotonin in the brain, turning the noradrenaline-using cells into serotonin-utilising cells. And because the team have discovered the factor that triggers this chemical identity switch, it may be possible to use this pathway to developed improved antidepressants that don't have the side effects of the drugs in current use.