Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New model for treatment of obsessive-compulsive disorder created

16.09.2011
Mouse model that replicates human OCD can point to more effective treatments

A new model of obsessive-compulsive disorder (OCD) that mirrors both symptoms of the disease and the timing of its treatment in humans has been created by University of Chicago researchers, according to a new study.

Using the model, researchers isolated a single neurotransmitter receptor in a specific brain region responsible for their model's OCD-like symptoms, offering new insight into the cause of the disorder. Further research with the model may point the way to new treatments for both OCD and autism, said Nancy Shanahan, PhD, lead author of the paper in Biological Psychiatry.

"Treatment for these people is greatly needed, and there really are very few highly valid animal models of the disorder," said Shanahan, a postdoctoral researcher at the University of Chicago. "Having one that seems to mimic the disorder so well, especially in terms of the time course of treatments that work in humans, is potentially very useful for researching novel therapeutics."

Stephanie Dulawa, PhD, assistant professor in the Department of Psychiatry and Behavioral Neuroscience at the University of Chicago Medical Center and senior author of the study, said, "Our model can make accurate predictions about what you see in OCD, and that gives us confidence that the underlying neurobiology is likely to be similar between the model and the actual disorder."

About 2.2 million people in the United States have been diagnosed with OCD, according to the National Institute of Mental Health. OCD patients struggle with repetitive rituals (such as hand-washing, counting and cleaning) and unwanted thoughts that can cause severe anxiety.

Psychiatrists have found some success treating patients with a class of drugs called serotonin reuptake inhibitors (SRIs) initially developed for depression. However, these drugs fail to reduce symptoms in as many as 60 percent of OCD patients and require four to eight weeks of treatment for therapeutic effects to begin.

"OCD is very mysterious and very prevalent," Shanahan said. "The development of OCD-specific treatments will be an extremely important step toward helping these people and preventing the disorder's cost to society."

With an animal model that replicates at least some aspects of OCD, researchers can dig deeper into the specific neurotransmitters and systems involved in the disorder. In Dulawa's laboratory, a team led by Shanahan found inspiration in a drug that activates the 1b class of receptors for the neurotransmitter serotonin. Clinically, the drug is used to treat migraines, but it is also known to have the unintended effect of increasing anxiety and compulsions in people with OCD.

When the drug was given to mice, they showed highly repetitive patterns of locomotion when placed into an open arena. The drug-treated mice also exhibited deficits in prepulse inhibition, a form of startle plasticity thought to measure the brain's ability to filter out intrusive thoughts, which plague OCD patients.

To determine whether these drug-induced behaviors reflected the neurobiology of OCD, the researchers tested the same drugs used to treat the disorder in humans. After four weeks of pre-treatment with SRIs — the same duration required to see therapeutic effects in humans — drug-induced OCD behaviors were reduced in the mice. Shorter SRI treatment or treatment with other antidepressant drugs that do not work in humans with OCD were unsuccessful in reducing the behaviors caused by the drug.

"We have this time course that nicely parallels or mimics the human therapeutic response," Shanahan said. "In order to study how these drugs are working and the pathophysiology of the disorder, we need a model where this delayed onset exists. So we are really excited about that."

The researchers then looked for a specific brain region where activation of 1b serotonin receptors creates OCD-like symptoms. In humans, scientists have identified a region called the orbitofrontal cortex that is more active in OCD subjects. Again matching the human data, selectively activating 1b receptors in the orbitofrontal cortex with the drug was sufficient to produce the OCD-like symptoms in the mice.

"We found that the 1b receptors in the orbitofrontal cortex were really the critical receptors," Dulawa said. "It was very affirming to our research because it is the brain region most heavily implicated in OCD throughout all of the human literature."

The results offer promising ideas about developing new treatments for OCD. A drug that blocks the serotonin 1b receptors may be effective in reducing OCD symptoms; however, no such chemical is currently available, Dulawa said. Alternatively, treating OCD patients with an activator of these receptors may exacerbate symptoms initially, but have long-term benefits as the number of serotonin 1b receptors decreases from over-stimulation.

"These treatments could potentially be much more specific and work much faster," Dulawa said. "Now that we have this model, we actually could pursue these ideas for better treatments in a disease where there is only one successful therapy."

The paper, "Essential role for orbitofrontal 5-HT1B receptors in OCD-like behavior and SRI response in mice," was published online September 15, 2011 by Biological Psychiatry (doi:10.1016/j.biopsych.2011.07.032). In addition to Shanahan and Dulawa, authors include Lady P. Velez of the University of Chicago and Virginia Masten of University of California, San Diego.

Funding for this work was provided by the National Institute of Mental Health.

For more news from the University of Chicago Medical Center, follow us on Twitter at @UChicagoMed, or visit our Facebook page at http://www.facebook.com/UChicagoMed, our research blog at http://sciencelife.uchospitals.edu, or our newsroom at http://www.uchospitals.edu/news/.

Robert Mitcum | EurekAlert!
Further information:
http://www.uchospitals.edu

More articles from Life Sciences:

nachricht First-of-its-kind chemical oscillator offers new level of molecular control
15.12.2017 | University of Texas at Austin

nachricht New technique could make captured carbon more valuable
15.12.2017 | DOE/Idaho National Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

New technique could make captured carbon more valuable

15.12.2017 | Life Sciences

First-of-its-kind chemical oscillator offers new level of molecular control

15.12.2017 | Life Sciences

A chip for environmental and health monitoring

15.12.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>