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Cocaine Studies Help Explain How Brain Regulates Hunger

Studies on the effects of cocaine in the brain have led to the discovery that feeding behavior and perhaps satiety is controlled at least in part by a novel group of naturally occurring brain peptides.

Specifically, the peptides inhibit food intake in animals and thus may be useful in developing medications to help treat obesity, bulimia and anorexia nervosa -- serious, yet common illnesses that can be life-threatening and are often at the root of various other health problems, such as diabetes and cardiovascular disease.

The findings of these studies, by neuroscientists at The Yerkes Primate Center, were presented this week at the annual meeting of the Society for Neuroscience in New Orleans.

The brain peptides are made from a mRNA transcript named CART, for Cocaine and Amphetamine Regulated Transcript. CART was found by examining changes in the brain following cocaine or amphetamine administration. Neuroscientist Pastor Couceyro was one of the first to notice CART mRNA increased with cocaine administration. Because they knew that behaviorally, cocaine use reduces food intake, the Yerkes team tested CART to see if it might be the agent responsible for the loss of appetite.

"When we injected the CART peptide into the brains of rats, their food intake was significantly inhibited -- by as much as 30 percent," explained Dr. Phil Lambert, who handled the behavioral aspect of the work. Similarly, when they blocked the brain's naturally-occurring CART peptides (by injecting antibodies which bind the to the peptides) the rats' feeding increased. "This antibody data is what makes us think CART is responsible in part for making you feel sated -- whether it's after eating, or after cocaine use."

When Yerkes scientists examined the location of CART peptides in the brain, they were in fact present in high levels in regions known to be involved in control of food intake. The next steps are to identify the precise structure of the CART peptides and to further explore their role in managing an animal's body weight.

"We are very excited about this new potential neurotransmitter link to feeding," Dr. Couceyro said. "We can keep one eye on the mechanisms of cocaine addiction and one eye on basic physiology governing hunger."

This could prove especially important to the 59 percent of Americans who, according to 1995 figures by the Institute of Medicine, are clinically obese.

Yerkes scientists caution that CART is only part of the feeding story. They believe there are many chemicals in the brain regulating food intake and if one is knocked out of commission, the brain will eventually learn to compensate. Eating is too important an activity to have just one neurotransmitter responsible. The Yerkes team is looking for a final common pathway for the food-related chemicals and their receptors.

"Examining food intake in humans is difficult because people don't necessarily eat just when they're hungry," Dr. Lambert explained, adding they are more dependent on social cues, timetables and taste than are animals. Generally, animals don't expend their energy unless they need to and eat only when hungry. However, if fed certain sweet mixtures, taste does tend to take over.