Wednesday, September 21, 2011

Mouse Model That Replicates Human OCD Can Point To More Effective Treatments

Jack Dikian
September 2011

Researchers at the University of Chicago are using a new model of obsessive-compulsive disorder (OCD) that mirrors both symptoms of the disease and the timing of its treatment in humans. In the paper published in Biological Psychiatry the researchers report that they have been able to use the model to 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.

Having a model 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. It’s possible that with further research the model may point the way to new treatments for both OCD and autism.

With a model that replicates aspects of OCD, researchers can dig deeper into the specific neurotransmitters and systems involved in the disorder. A drug that is used to treat migraines, but also known to have the unintended effect of increasing anxiety and compulsions in people with OCD was shown to bring about highly repetitive patterns of locomotion in mice.

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.

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.

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 according to the researchers.


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

Nancy Shanahan, PhD, lead author of the paper in Biological Psychiatry

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