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U of C researchers create new model of obsessive-compulsive disorder

September 15, 2019

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."

Source: University of Chicago Medical Center