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July 10 , 2006
Key brain receptors may help in creating addiction, obesity drugs

BY megan Jentz

Researchers at Yerkes National Primate Research Center have discovered a key brain receptor chemical that’s paving the way for a new class of drugs targeting addiction and obesity. This finding could have a significant economic impact on health care costs in the United States as health problems associated with drug addiction and obesity currently set Americans back billions of dollars each year.

The study, led by Aleksandra Vicentic, assistant research professor in Yerkes’ neuroscience division, and Michael Kuhar, chief of the neuroscience division, is the first to find evidence for specific cocaine- and amphetamine-regulated transcript (CART) peptide receptor binding. Given the role of CART peptides in feeding, stress and psychostimulant drug action, this will facilitate the search for therapeutic agents to imitate or block the actions of CART peptides. These findings were presented at the 68th annual meeting of the College on Problems of Drug Dependence in Scottsdale, Ariz.

Serving as chemical messengers, CART peptides (CART 55-102 and CART 62-102) are neurotransmitters and endocrine factors in the nervous system and periphery that have been implicated in the regulation of feeding, body weight, drug reward and stress. Clear evidence for behavioral and cellular activity of the peptides has existed for years, but the receptors had yet to be found until Yerkes researchers recently discovered evidence for specific receptor binding.

“Receptors are entry into the pharmacology world, and we now have an assay, or a chemical analysis, for the CART receptor,” said Kuhar. “Because we have identified the receptor, we can look for chemicals that interrupt or mimic the binding to the receptor, in the hope of finding molecules to target as possible therapies for obesity, cocaine addiction and other disorders regulated by the CART peptide.”

“Identifying the receptor also shows promise for the use of high through-put methods of drug screening, a process where hundreds of thousands of molecules can be screened for pharmacological use as either mimics of the CART peptide or as blockers for the receptors,” said Vicentic. “While CART peptides are not practical therapeutic agents, identifying the receptor is particularly important as it modulates stress, feeding and addiction.”

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