A Duke University study, appearing in the online journal Biological Psychiatry, has linked a single chemical receptor in the brain to a range of OCD-like symptoms in laboratory mice.
“These new findings are enormously hopeful for considering how to approach neuro-developmental diseases, and behavioral and thought disorders,” said senior investigator Nicole Calakos, M.D., Ph.D.
OCD, or obsessive-compulsive disorder, is characterized by intrusive, obsessive thoughts that generate anxiety, and compulsive, repetitive behaviors that temporarily mitigate the anxiety. The disorder affects approximately 3.3 million people in the U.S.
The Duke research offers a new mechanistic understanding of OCD, and implies a class of previously investigated drugs may provide symptom relief.
The recent investigation is based on a 2007 Duke study that developed a novel mouse model of OCD by eliminating a gene that codes for a protein called Sapap3. The Sapap3 protein helps organize connections between neurons so that cells can exchange information.
Mice that lacked the Sapap3 protein demonstrated signs of anxiety, and began grooming excessively—behavior remarkably similar to the excessive hand washing demonstrated by some OCD sufferers. However, it was unclear how an absence of the Sapap3 gene triggered the grooming behaviors.
The more recent Duke research revealed that an over-active neurotransmitter receptor, called mGluR5, fueled the obsessive mouse activity. When this receptor was chemically blocked, the rodent’s abnormal grooming and anxiety behaviors quickly stopped.
“The reversibility of the symptoms was immediate - on a minute time frame,” said Calakos.
The researchers also found that giving normal lab mice a drug elevating mGluR5 activity produced the identical compulsive grooming and anxiety behaviors observed in the Sapap3-lacking mice.
In brains without a functioning Sapap3 protein, according to Calakos and colleagues, the mGluR5 receptor is always turned on, and over-stimulates brain centers involved with compulsive actions. This suggests that mGluR5 should be considered when treating OCD. “But [for] which people and which compulsive behaviors? We don’t know yet,” noted Calakos.
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