How Antidepressants Work - I

In a recent article in the journal Science, researchers working in Italy announced that giving laboratory rats fluoxetine (AKA: Prozac)had the effect of turning on the development of brain cells in the visual area of the animals’ brains. You may be asking yourself “What does that have to do with making depression better!?” If so, you are probably still thinking about mood disorders as “chemical imbalances.” Well, that idea is so-o-o 20th Century! There is now a lot of evidence that new brain cells (neurons) are constantly being born in certain areas of the the brain (the most important is the hippocampus) and that the growth and development of these new cells is needed for normal mood control. One way to think about this process is that this area of the brain must constantly reprogram itself by bringing new neurons on line and making and re-making the connections between these new and the older neurons. The ability to do this remodeling is called neuroplasticity (remember that the original definition of “plastic” is “capable of being molded, or of receiving form.”

These researchers took advantage of a well-known fact regarding the development of the brain’s visual system, namely that this brain area needs visual stimulation just after birth to develop properly. If the visual cortex does not receive this stimulation, this area of the brain doesn’t organize its connections properly and individuals cannot see properly. You may have heard of “lazy eye” (amblyopia) being treated in children by covering their “good” eye with a patch, essentially over-stimulating the “lazy” eye so it can catch up. It’s important to know that the “catching up” happens in the brain, not the eyeball. Also, as individuals mature, this ability to catch up is lost. This brain area loses its plasticity. It used to be thought that the ability of the visual area of the brain to organize in response to this stimulation (its plasticity) completely and irretrievably disappeared in adulthood.

These researchers artificially created a “lazy eye” problem (really, for the reasons stated above, it should be called “lazy brain” or better yet: “lazy visual cortex”) in young rats by covering one of their eyes. As the rats approached adulthood, they gave some of them fluoxetine for several weeks, and they switched the eye patch to the other eye in all the rats. In the rats that did not receive the antidepressant, the artificially created “lazy visual cortex” never recovered when the eye was uncovered. The brain had lost its plasticity, and could no longer respond to the signals from the now opened eye. The rats that had received the antidepressant for two weeks, on the other hand, recovered their vision completely! The fluoxetine had turned on the brain’s ability to adapt. Brain plasticity was restored.

It’s been hypothesized for some years that antidepressants increased plasticity in the hippocampus, but it’s been hard to measure this increase. This study is different, because the researchers looked at an area of the brain (the visual cortex) that completely loses its plasticity in adulthood. Proving that antidepressant treatment restored plasticity to this brain area in adult brains is further evidence that this process is crucial to how antidepressants work.