Research gives new insight into how antidepressants work in the brain

November 8, 2013, Oregon Health & Science University

(Medical Xpress)—Research from Oregon Health & Science University's Vollum Institute, published in the current issue of Nature, is giving scientists a never-before-seen view of how nerve cells communicate with each other. That new view can give scientists a better understanding of how antidepressants work in the human brain—and could lead to the development of better antidepressants with few or no side effects.

The article in today's edition of Nature came from the lab of Eric Gouaux, Ph.D., a senior scientist at OHSU's Vollum Institute and a Howard Hughes Medical Institute Investigator. The article describes research that gives a better view of the structural biology of a protein that controls communication between nerve cells. The view is obtained through special structural and biochemical methods Gouaux uses to investigate these neural proteins.

The Nature article focuses on the structure of the dopamine transporter, which helps regulate dopamine levels in the brain. Dopamine is an essential neurotransmitter for the human body's central nervous system; abnormal levels of dopamine are present in a range of neurological disorders, including Parkinson's disease, drug addiction, depression and schizophrenia. Along with dopamine, the neurotransmitters noradrenaline and serotonin are transported by related transporters, which can be studied with greater accuracy based on the dopamine transporter structure.

The Gouaux lab's more detailed view of the dopamine transporter structure better reveals how anti-depressants act on the transporters and thus do their work.

The more detailed view could help scientists and pharmaceutical companies develop drugs that do a much better job of targeting what they're trying to target—and not create side effects caused by a broader blast at the brain proteins.

"By learning as much as possible about the structure of the transporter and its complexes with antidepressants, we have laid the foundation for the design of new molecules with better therapeutic profiles and, hopefully, with fewer deleterious ," said Gouaux.

Gouaux's latest dopamine transporter research is also important because it was done using the molecule from fruit flies, a dopamine transporter that is much more similar to those in humans than the bacteria models that previous studies had used.

The dopamine transporter article was one of two articles Gouaux had published in today's edition of Nature. The other article also dealt with a modified amino acid transporter that mimics the mammalian neurotransmitter transporter proteins targeted by antidepressants. It gives new insights into the pharmacology of four different classes of widely used antidepressants that act on certain transporter proteins, including transporters for dopamine, serotonin and noradrenaline. The second paper in part was validated by findings of the first paper—in how an antidepressant bound itself to a specific transporter.

"What we ended up finding with this research was complementary and mutually reinforcing with the other work—so that was really important," Gouaux said. "And it told us a great deal about how these transporters work and how they interact with the antidepressant molecules."

Gouaux's discoveries over the years in neurotransmission have established him as one of the top investigators in his field. His research has important implications for understanding the mechanisms of not just , but also drugs used for the treatment of a wide range of psychiatric and neurological diseases.

Explore further: Long-term ADHD treatment increases brain dopamine transporter levels, may affect drug efficacy

Related Stories

Long-term ADHD treatment increases brain dopamine transporter levels, may affect drug efficacy

May 15, 2013
Long-term treatment of attention deficit/hyperactivity disorder (ADHD) with certain stimulant medications may alter the density of the dopamine transporter, according to research published May 15 in the open access journal ...

'Traffic' in our cells works both for and against us

May 1, 2013
A mechanism that permits essential substances to enter our cells while at the same time removing from them harmful components also has a "down side." This negative aspect prevents vital drugs, such as anti-cancer drugs, from ...

Challenging Parkinson's dogma

October 24, 2012
Scientists may have discovered why the standard treatment for Parkinson's disease is often effective for only a limited period of time. Their research could lead to a better understanding of many brain disorders, from drug ...

Discovery could reduce chemotherapy's side effects

March 11, 2012
A team of researchers at Duke University has determined the structure of a key molecule that can carry chemotherapy and anti-viral drugs into cells, which could help to create more effective drugs with fewer effects to healthy ...

Compound enhances SSRI antidepressant's effects in mice

June 21, 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 ...

Recommended for you

Researchers illustrate how muscle growth inhibitor is activated, could aid in treating ALS

January 19, 2018
Researchers at the University of Cincinnati (UC) College of Medicine are part of an international team that has identified how the inactive or latent form of GDF8, a signaling protein also known as myostatin responsible for ...

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

beleg
not rated yet Nov 08, 2013
Is GLXY-13 finishing the last of it's clinical trials leading the antidepressant research here?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.