Eating An investigation of the brain circuits behind compulsive behavior has surprisingly revealed they may be intimately linked to circuits that control obesity. The US researchers say the discovery offers new insights into the development and treatment of both compulsive behavior and eating disorders.

Study leaders and neuro-psychiatrists Michael Lutter and Andrew Pieper of the University of Iowa (UI), and colleagues, write about their work in this week’s online early edition of the Proceedings of the National Academy of Sciences (PNAS) .

They describe how they bred mice missing a gene known to cause obesity, and suspected of being involved in compulsive behavior, and mated them with mice bred to have compulsive grooming and were surprised to see offspring that were neither obese nor compulsive groomers.

They say this shows the brain circuits that control obsessive-compulsive behavior are meshed with circuits that control food intake and body weight: a finding that will have implications for treating the compulsive behavior in many psychiatric diseases like obsessive-compulsive disorder (OCD), Tourette syndrome, and eating disorders.

Obese Mice and Compulsive Groomers

The researchers worked with two types of mice engineered for studying human disorders: one bred to study compulsive behavior (Pieper’s field of interest), and the other bred to study an inherited form of obesity (Lutter’s specialism).

The compulsive behavior mice are missing a brain protein called SAPAP3, the lack of which causes them to groom themselves excessively. The behavior can be effectively controlled with fluoxetine, a drug commonly used to treat OCD in people.

The inherited obesity mice lack a brain protein called MC4R. Mutations in the MC4R gene are the biggest single-gene cause of over-eating and morbid obesity in people.

Lutter, an assistant professor of psychiatry at the UI Carver College of Medicine, is interested in MC4R signaling pathways and how they affect the development of obesity.

“I’m also interested in how these same molecules affect mood and anxiety and reward, because it’s known that there is a connection between depression and anxiety and development of obesity,” he explains in a statement.

What Happened When the Two Strains Interbred

Lutter and Pieper, who is an associate professor of psychiatry and neurology at Carver, were aware of an old study that suggested MC4R might play a role not only in food intake and obesity, but also in compulsive behavior, so they decided to test the idea, as Lutter explains:

“We knew in one mouse you could stimulate excessive grooming through this MC4R pathway and in another mouse a different pathway (SAPAP3) caused compulsive grooming.”

“So, we decided to breed the two mice together to see if it would have an effect on compulsive grooming,” he adds.

The breeding experiment bore out their hypothesis: knocking out the MC4R protein in OCD mice lacking SAPAP3 normalized their grooming behavior. And they also found chemically blocking the protein had the same effect, which was mirrored by normal patterns in brain cell communication linked to compulsive behavior.

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