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Researchers Learn How Prozac Works

Despite having been used for over 30 years, the pharmacological action of antidepressants such as Prozac has remained obscure.

European research published this week sheds new light on the mechanisms of action of these drugs.

In particular, the researchers have revealed, for the first time, a sequence of reactions caused by Prozac at the neuron level, which contributes to an increase in the amounts of serotonin, a chemical “messenger” essential to the brain, and deficient in depressive individuals.

Details of this work are published in the journal Science.

Depressive states are associated with a deficit of serotonin (5-HT), one of the neurotransmitters essential for communication between neurons and particularly involved in eating and sexual behaviors, the sleep-wake cycle, pain, anxiety and mood problems.

Strategies employing antidepressant class I molecules, developed since the 1960s are thus primarily aimed at increasing the quantity of serotonin released in the synaptic gap, the space between two neurons, where the nervous communications take place via the neurotransmitters.

Although it has been known for several years that antidepressants like Prozac have the effect of increasing the concentration of serotonin by blocking its recapture by the serotonin transporter (SERT) in the synapses, it was not previously known how to explain the three-week delay in their action.

Research teams have now characterized, for the first time, in vitro and then in vivo, the various reactions and intermediate molecules produced in the presence of Prozac, which are eventually responsible for an increased release of serotonin.

In particular, the researchers have identified the key role of one particular microRNA in the active mechanisms of the antidepressants on the brain.

This microRNA, known as miR-16, controls synthesis of the serotonin transporter.

Under normal physiological conditions, this transporter is present in the so-called “serotonergic” neurons, i.e. neurons specialised in production of this neurotransmitter. However, expression of this transporter is reduced to zero by miR-16 in so-called “noradrenaline” neurons, another neurotransmitter involved in attention, emotions, sleep, dreaming and learning.

In response to Prozac, the serotonergic neurons release a signal molecule, which causes the quantity of miR-16 to drop, which unlocks expression of the serotonin transporter in the noradrenaline neurons.

These neurons become sensitive to Prozac. They continue to produce noradrenaline, but they become mixed: they also synthesize serotonin. Ultimately, the quantity of released serotonin is increased both in the serotonergic neurons, via the direct effect of the Prozac which prevents its recapture, and in the noradrenaline neurons through the reduction of miR-16.

According to the researchers, this means that antidepressants are able to activate a new ‘source’ of serotonin in the brain.

“Furthermore, our results demonstrate that the effectiveness of Prozac rests on the ‘plastic’ properties of the noradrenaline neurons, i.e. their capacity to acquire the functions of serotonergic neurons.”

These results open up new avenues of research for the treatment of depressive states.

Source: INSERM (Institut national de la santé et de la recherche médicale)

Researchers Learn How Prozac Works

Rick Nauert PhD

Rick Nauert, PhDDr. Rick Nauert has over 25 years experience in clinical, administrative and academic healthcare. He is currently an associate professor for Rocky Mountain University of Health Professionals doctoral program in health promotion and wellness. Dr. Nauert began his career as a clinical physical therapist and served as a regional manager for a publicly traded multidisciplinary rehabilitation agency for 12 years. He has masters degrees in health-fitness management and healthcare administration and a doctoral degree from The University of Texas at Austin focused on health care informatics, health administration, health education and health policy. His research efforts included the area of telehealth with a specialty in disease management.

APA Reference
Nauert PhD, R. (2015). Researchers Learn How Prozac Works. Psych Central. Retrieved on November 21, 2018, from https://psychcentral.com/news/2010/09/17/researchers-learn-how-prozac-works/18336.html

 

Scientifically Reviewed
Last updated: 6 Oct 2015
Last reviewed: By John M. Grohol, Psy.D. on 6 Oct 2015
Published on PsychCentral.com. All rights reserved.