Researchers Report How Popular Antidepressant Can Reseal Brain

Prozac^®, the trade name of the drug fluoxetine, was introduced to the US market for the treatment of depression in 1988. Thirty years later, scientists still did not know exactly how the drug exerted its effects on mood. At present, the researchers report that in addition to the known action of the drug on the serotonin receptors, fluoxetine could reorganize the nerve fibers in the hippocampus of the mouse brain. They report their results in ACS Chemical Neuroscience.

Fluoxetine was the first drug in the clbad of compounds called selective serotonin reuptake inhibitors (SSRIs) to have been approved by the US Food and Drug Administration. SSRIs are thought to act primarily by increasing the amount of neurotransmitter serotonin available for signaling between neurons, but researchers suspected that other processes might be ongoing. In previous studies, Mbadimo Pasqualetti and colleagues have shown that genetic exhaustion and the restoration of serotonin in mice can rearrange the nerve fibers of the hippocampus. Now, they wanted to see if the more subtle changes in serotonin availability caused by fluoxetine treatment could have the same effect.

To find out, the team used a mouse model that expresses green fluorescent protein (GFP) in the neurons that produce serotonin in the brain. They administered fluoxetine to these mice in their drinking water for 28 days, then compared the GFP signals in their brains to those of control mice to which the drug had not been administered. Mice taking fluoxetine had fewer serotonin-producing nerve fibers and smaller diameter than control mice, but only in the hippocampus. Although the consequences of this structural rearrangement are currently unknown, this could contribute to the way in which antidepressants exert their therapeutic effect, according to the researchers.