Compound enhances SSRI antidepressant's effects in mice

June 20, 2013

SAN ANTONIO (June 20, 2013) -- A synthetic compound is able to turn off "secondary" vacuum cleaners in the brain that take up serotonin, resulting in the "happy" chemical being more plentiful, scientists from the School of Medicine at The University of Texas Health Science Center San Antonio have discovered. Their study, released June 18 by The Journal of Neuroscience, points to novel targets to treat depression.

Serotonin, a neurotransmitter that carries chemical signals, is associated with feelings of wellness. Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants that block a specific "vacuum cleaner" for serotonin (the serotonin transporter, or SERT) from taking up serotonin, resulting in more supply of the neurotransmitter in circulation in the extracellular fluid of the brain.

Delicate balance

"Serotonin is released by neurons in the brain," said Lyn Daws, Ph.D., professor of physiology and pharmacology in the School of Medicine. "Too much or too little may be a bad thing. It is thought that having too little serotonin is linked to depression. That's why we think Prozac-type drugs (SSRIs) work, by stopping the serotonin transporter from taking up serotonin from extracellular fluid in the brain."

A problem with SSRIs is that many depressed patients experience modest or no therapeutic benefit. It turns out that, while SSRIs block the activity of the serotonin transporter, they don't block other "vacuum cleaners." "Until now we did not appreciate the presence of backup cleaners for serotonin," Dr. Daws said. "We were not the first to show their presence in the brain, but we were among the first show that they were limiting the ability of the SSRIs to increase serotonin signaling in the brain. The study described in this new paper is the first demonstration of enhancing the antidepressant-like effect of an SSRI by concurrently blocking these backup vacuum cleaners."

Serotonin ceiling

Even if SERT activity is blocked, the backup vacuum cleaners (called organic cation transporters) keep a ceiling on how high the serotonin levels can rise, which likely limits the optimal therapeutic benefit to the patient, Dr. Daws said.

"Right now, the compound we have, decynium-22, is not an agent that we want to give to people in clinical trials," she said. "We are not there yet. Where we are is being able to use this compound to identify new targets in the brain for antidepressant activity and to turn to medicinal chemists to design molecules to block these secondary vacuum cleaners."
-end-
This work was supported by National Institutes of Health Grants R01-MH064489 (L.C.D.), R01-MH093320 (L.C.D., W.K.) and R03-MH086708 (G.G.G.), and a National Alliance for Research on Schizophrenia and Depression Independent Investigator Award (L.C.D.).

Decynium-22 Enhances SSRI-Induced Antidepressant-Like Effects in Mice: Uncovering Novel Targets to Treat Depression Rebecca E. Horton 1 Deana M. Apple 1,2 W. Anthony Owens 1 Nicole L. Baganz 1 Sonia Cano 2 Nathan C. Mitchell 1 Melissa Vitela 1 Georgianna G. Gould 1 Wouter Koek 2,3* and Lynette C. Daws 1,3*
1 Departments of Physiology, 2 Psychiatry, and 3 Pharmacology, University of Texas Health Science Center, San Antonio, Texas 78229-3900

For current news from the UT Health Science Center San Antonio, please visit our news release website, like us on Facebook or follow us on Twitter.

About the UT Health Science Center San Antonio

The University of Texas Health Science Center at San Antonio, one of the country's leading health sciences universities, ranks in the top 3 percent of all institutions worldwide receiving National Institutes of Health funding. The university's schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced approximately 28,000 graduates. The $736 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways "We make lives better®," visit http://www.uthscsa.edu.

University of Texas Health Science Center at San Antonio

Related Serotonin Articles from Brightsurf:

First look at how hallucinogens bind structurally to serotonin receptors
Although hallucinogenic drugs have been studied for decades, little is known about the underlying mechanisms in the brain by which they induce their effects.

Guilt by dissociation: Study sheds light on serotonin in autism
A study on serotonin, a mood-regulating molecule in the brain that regulates many brain synapses, is helping to unravel the puzzle surrounding its role in autism.

How serotonin balances communication within the brain
Our brain is steadily engaged in soliloquies. These internal communications are usually also bombarded with external sensory events.

Why do we freeze when startled? New study in flies points to serotonin
A Columbia University study in fruit flies has identified serotonin as a chemical that triggers the body's startle response, the automatic deer-in-the-headlights reflex that freezes the body momentarily in response to a potential threat.

Settling the debate on serotonin's role in sleep
New research finds that serotonin is necessary for sleep, settling a long-standing controversy.

Whole grain can contribute to health by changing intestinal serotonin production
Adults consuming whole grain rye have lower plasma serotonin levels than people eating low-fibre wheat bread, according to a recent study by the University of Eastern Finland and the International Agency for Research on Cancer (IARC).

Serotonin boosts neuronal powerplants protecting against stress
Research from the Vaidya and Kolthur-Seetharam groups (TIFR) shows that the neurotransmitter serotonin enhances the production and functions of neuronal mitochondria, the powerhouse of the cell, and protect against stress.

Fight or flight: Serotonin neurons prompt brain to make the right call
Known for its role in relieving depression, the neurochemical serotonin may also help the brain execute instantaneous, appropriate behaviors in emergency situations, according to a new Cornell study published Feb.

New images show serotonin activating its receptor for first time
A team of researchers from Case Western Reserve University School of Medicine have used high-powered microscopes to view serotonin activating its receptor for the first time.

Serotonin-Noradrenalin reuptake inhibitors may cause dependence and withdrawal when stopped
The difficulties that people have in discontinuing antidepressant medications has been in the news recently.

Read More: Serotonin News and Serotonin Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.