Summary: Researchers have identified a new therapeutic target to help treat compulsive binge eating.
Source: Boston University Medical Center.
Study may provide better understanding of disorder, possible treatments.
A new therapeutic target for the treatment of compulsive binge eating has been identified by researchers at Boston University School of Medicine (BUSM).
The study, which is published in the journal Neuropsychopharmacology, reports the beneficial effects of the activation of a class of receptors, Trace Amine-Associated Receptor 1 (TAAR1), on compulsive, binge eating. TAAR1 discovered in 2001, is a receptor that binds molecules in the brain called trace amines.
Compulsive, binge eating is estimated to affect approximately 15 million people suffering from forms of obesity and eating disorders in the United States. It is characterized by episodes of eating large quantities of food, often very quickly and to the point of discomfort. Binge eaters often experience a loss of control during the binge as well as shame, distress or guilt afterwards.
This study has important implications for the treatment of all the disorders which are characterized by compulsive, binge eating. “Effective therapeutic treatments currently available are very elusive. The results of this study provide a new window toward the development of a new class of drugs with a novel target unexplored until now,” said corresponding author Pietro Cottone, PhD, co-director of the Laboratory of Addictive Disorders (LAD) and associate professor of pharmacology and psychiatry at BUSM.
Researchers created an experimental model that developed an addiction-like binge eating behavior to sugary, chocolate-flavored food intake as compared to the controls. The experimental model was also more prone to cues associated with the food and exhibited risky behavior to obtain it, while the control group did not.
They then tested whether administering a TAAR1 agonist, RO5256390, could reduce the maladaptive feeding behaviors. “Our data show that RO5256390 was able to block binge eating of the sugary diet, blocked the strength of cues associated with junk food and blocked compulsive eating in a potentially unsafe environment,” explained co-first author of the study Antonio Ferragud, PhD, postdoctoral fellow in the LAD.
The researchers observed that TAAR1 was decreased in the region of the brain important for the process of decision-making and executive function (infralimbic cortex) of the experimental models as compared to controls. “TAAR1 seems to be working as a “brake” in the areas of the brain involved in decision making and executive function. Subjects exposed to junk food lose this “brake” and show aberrant addiction-like behavior over food. We are able to restore the function by activating this receptor,” added Adam Howell, MS, co-first author of the study and master fellow in the LAD.
Other BUSM contributors included: Catherine Moore, Tina Ta, and Valentina Sabino PhD, co-director of the LAD and associate professor of pharmacology and psychiatry at BUSM. Marius Hoener, PhD, from Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland were also a co-authors.
Funding: Research was supported by the National Institute on Drug Abuse, National Institute of Mental Health, the Peter Paul Career Development Professorship, the McManus Charitable Trust, and Boston University’s Undergraduate Research Opportunities Program (UROP).
Source: Gina DiGravio – Boston University Medical Center
Image Source: NeuroscienceNews.com image is credited to Juliet Davidow/Shohamy Lab, Columbia University Mortimer B. Zuckerman Mind Brain Behavior Institute.
Original Research: Abstract for “The Trace Amine-Associated Receptor 1 Agonist RO5256390 Blocks Compulsive, Binge-Like Eating in Rats” by Antonio Ferragud, Adam D Howell, Catherine F Moore, Tina L Ta, Marius C Hoener, Valentina Sabino and Pietro Cottone in Neuropsychopharmacology. Published online August 15 2016 doi:10.1038/npp.2016.233
The Trace Amine-Associated Receptor 1 Agonist RO5256390 Blocks Compulsive, Binge-Like Eating in Rats
Compulsive, binge eating of highly palatable food constitutes a core feature of some forms of obesity and eating disorders, as well as of the recently proposed disorder of food addiction. Trace Amine-Associated Receptor 1 (TAAR1) is a highly conserved G-protein-coupled receptor bound by endogenous trace amines. TAAR1 agonists have been shown to reduce multiple behavioral effects of drugs of abuse through their actions on the mesocorticolimbic system. In this study, we hypothesized that TAAR1 may play a role in compulsive, binge-like eating; we tested this hypothesis by assessing the effects of a TAAR1 agonist, RO5256390, in multiple excessive feeding-related behaviors induced by limiting access to a highly palatable diet in rats. Our results show that RO5256390 blocked binge-like eating in rats responding 1 h/day for a highly palatable sugary diet. Consistent with a palatability-selective effect, drug treatment selectively reduced the rate and regularity of palatable food responding, but it did not affect either baseline intake or food restriction-induced overeating of the standard chow diet. Furthermore, RO5256390 fully blocked compulsive-like eating when the palatable diet was offered in an aversive compartment of a light/dark conflict box, and blocked the conditioned rewarding properties of palatable food, as well as palatable food-seeking behavior in a second-order schedule of reinforcement. Drug treatment had no effect on either anxiety-like or depressive-like behavior, and it did not affect control performance in any of the tests. Importantly, rats exposed to palatable food showed decreased TAAR1 levels in the medial prefrontal cortex (mPFC), and RO5256390 microinfused into the infralimbic, but not prelimbic, subregion of the mPFC reduced binge-like eating. Altogether, these results provide evidence for TAAR1 agonism as a novel pharmacological treatment for compulsive, binge eating.
“The Trace Amine-Associated Receptor 1 Agonist RO5256390 Blocks Compulsive, Binge-Like Eating in Rats” by Antonio Ferragud, Adam D Howell, Catherine F Moore, Tina L Ta, Marius C Hoener, Valentina Sabino and Pietro Cottone in Neuropsychopharmacology. Published online August 15 2016 doi:10.1038/npp.2016.233