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Can anti-depressants change brain circuitry?

The therapeutic activity of Prozac (Fluoxetine), a widely used anti-depressant, includes more than changes in serotonin levels, study shows.

Serotonin or 5-hydroxytryptamine (5-HT) is a chemical produced in the brain and intestines. It is a neurotransmitter that transmits chemical messages between different parts of the brain. Serotonin is thought to regulate mood, appetite, and sleep, amongst many other functions of the body. Low levels of serotonin are linked to mood disorders such as depression. One of the most widely prescribed medications for the treatment of depression, Prozac, targets serotonin levels in the brain.

Prozac (Fluoxetine) belongs to the class of drugs known as SSRIs (selective serotonin reuptake inhibitors) that increase the levels of serotonin available by reducing the reabsorption of serotonin by nerve cells. Patients suffering from depression have low levels of serotonin. However, the causal link between serotonin and depression has not been clearly established and is just one part of the puzzle in understanding the causes of depression. Studies have also shown that brain structure in these patients is also altered. These patients have smaller hippocampi, a part of the brain related to memory and emotions, due to shrinkage of the neurons and loss of connections between nerve cells in this brain region.

The therapeutic effect of SSRIs includes stimulating neuroplasticity – changes in the properties and functions of areas in the brain in response to changes in the environment. The hippocampus is one of the brain regions affected by SSRIs. The hippocampus is rich in nerve cells that produce serotonin as well as receptors for serotonin. Researchers from the University of Pisa, Italy had shown in earlier studies that genetically inactivating the production of serotonin increases the density of serotonin-producing nerve fibres in the hippocampus. Next, they probed if prolonged use of fluoxetine also leads to neuroplastic changes in the hippocampus. The results of their study were recently published in ACS Chemical Neuroscience.

The team of researchers led by Dr. Pasqualetti found that mice that were given fluoxetine for 28 days had a decrease in the density of serotonin-producing nerve fibers in their hippocampi. They ruled out the possibility that this reduction was due to changes in the genetic activity of the serotonin-producing gene. Instead, it is an example of the neuroplasticity of the brain showing that the brain is capable of bi-directional changes in response to the lower or higher levels of serotonin available. This study provides an elegant example of the malleability of the brain structure in response to changes in its environment and is also the first to report changes in serotonin circuitry linked to the use of SSRIs.

Written by Bhavana Achary, Ph.D

References: Nazzi S, Maddaloni G, Pratelli M, Pasqualetti M. Fluoxetine Induces Morphological Rearrangements of Serotonergic Fibers in the Hippocampus. ACS Chem Neurosci. 2019 Jul 17;10(7):3218-3224

Bhavana Achary PhD
Bhavana Achary PhD
Bhavana Achary completed her Ph.D in Molecular Biology and Biochemistry at the Pennsylvania State Universisty, USA, studying gene regulation. Pivoting from the bench to the writer's desk, Bhavana hopes to bring the advances in science and health research to a broader audience while maintaining the scientific rigour and knowledge gained over her years in research. She enjoys the opportunity to keep abreast of the latest in medical research while also making it more accessible to a lay audience. Currently based in Singapore, Bhavana enjoys exploring the Southeast Asian region.
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