FOOD FIX

Neurobiology Highlights Similarities Between Obesity and Drug Addiction

It was 1990, and Neal, a 55-year-old salesman from Silver Spring,
Md., was hitting rock bottom. For years, he had soothed the stress of
his chaotic life with an evening bowl of vanilla ice cream. But in
time, that just wasn't enough. Neal started adding a second bowl,
then a third. Even after he'd moved on to wolfing down an entire
gallon in a single sitting, he soon needed yet a bigger fix. He added
doughnutsa "one, two, then an entire box.

Neal's not-so-sweet nightly habit eventually blew his weight up to
350 pounds. What he gained in size, he lost in other parts of his
life: His marriage fell apart, he lost his job, and he spent his
nights wondering whether his persistent chest pain meant that he'd
die before morning. As his life spiraled downward, he spoke to a
friend who was a recovering alcoholic.

"When he was telling me the story about what he was doing with
alcohol, I could see that's what I was doing with food, how I was
using it," Neal says. At the time, he says, food seemed like an
innocuous fixa "it was hard for him to imagine overdosing on ice
cream and doughnuts. "But if it wasn't food," he adds, "then it would
have been cocaine, heroin, alcohol, or something else for me."

Many people have suspected that addiction underlies much of obesity.
In fact, in 1960, an overweight woman started a weight-loss group
that used a 12-step program modeled after that of Alcoholics
Anonymous. Neal turned to Overeaters Anonymous and has since lost
more than 100 pounds. Several other groups use 12-step programs to
deal with overeating.

In recent years, scientists have discovered neurological connections
between overeating and drug addiction. They've conducted studies
showing that the brains of individuals with either of these
conditions differ from other people's brains in similar ways. The
researchers have also described a few enlightening differences
between the brains of overeaters and those of drug abusers.

Understanding the neurological causes of overeating and drug
addiction, say the researchers, could lead to new treatments for both
conditions.

Filling a Void

Overeating and drug addiction probably come from ancient roots but
have taken a modern twist, says Roy Wise of the National Institute on
Drug Abuse (NIDA) in Bethesda, Md. He and others espouse the
hypothesis that these problems have arisen as a by-product of the
brain circuitry that motivated our ancestors to find sustenance,
mates, and other necessities that enhanced the long-term success of
the species.

"The brain circuitry that we use to find drugs or food has the same
mechanisms involved in looking for anything rewarding," says Wise.

As humans became more adept at manipulating their material world,
people recognized and later created substances that especially
satisfy these reward-seeking brain circuits. A similar situation has
turned up in recent history with food, says Wise: As the availability
of cheap, tasty food has skyrocketed, so has the number of people who
are obese as a result of overeating.

Nora Volkow, the director of NIDA, agrees. "When you hunt animals,
you may succeed or not. But when you open the fridge, you will
succeed 100 percent of the time," she says.

Volkow wants to know why some people can't seem to close the fridge.
"Is the signal [to eat] really stronger in overeaters, or is the part
of the brain controlling these urges not normal?" she asks. She and
her collaborators began to answer this question in 2001, when they
studied differences between the brains of normal-weight and of obese people.

In previous research that had focused solely on drug abusers, Volkow
and other researchers found that many addicts had a deficiency in a
particular type of receptor for dopamine, one of the brain's
feel-good chemicals. Most drugs of abuse reward their takersa "and
reinforce the habita "by flooding the brain with more dopamine than
normal. So, the researchers theorized that some drug users become
addicts as a way of making up for a shortage of dopamine receptors.

Scientists have known for decades that eating also floods the brain
with dopamine. When Volkow and her colleagues looked at the brains of
10 obese people, the team found a dopamine-receptor deficiency
identical to that in drug addicts. Volkow stresses that obesity seems
to be a significantly more complex disorder than drug abuse because
many unrelated factors, such as glandular problems, lack of exercise,
or a genetic predisposition to storing fat, can lead to weight gain
(SN: 4/2/05, p. 216:
http://www.sciencenews.org/articles/20050402/bob9.asp). However, the
brains of several of the obese volunteers in Volkow's study seemed to
be telling another story: "These people were compulsively driven to
eat as if food were their stimulus of choice," she says.

Constant Craving

A more recent study sheds light on the mechanism behind cravings,
whether they be for illicit drugs or specific foods.

In the past decade, many studies have sought the identity of the
brain areas and chemical signals that trigger drug cravingsa
"information that could eventually result in pharmaceuticals that
help addicts stick to treatment programs. However, notes Marcia
Pelchat of the Monell Chemical Senses Center in Philadelphia, hardly
any neurological studies have focused on food cravings.

Pelchat and her colleagues designed a study that separated food
cravings from hunger by denying people desired foods but keeping them satiated.

At the beginning of the study, the scientists asked each person to
name a couple of foods that he or she "really liked." Then, the
researchers gave some study subjects as many nutritionally complete
vanilla shakes as they could eat, but nothing else. Other subjects
could eat whatever and as much as they wanted, including the shakes.

After keeping 20 people on one of the two diets for a day and a half,
Pelchat's team gave each of the subjects a functional magnetic
resonance imaging (fMRI) scan, which measures brain activity. During
the scan, the researchers flashed the names of the volunteers'
favorite foods on a screen, alternating them with the brand name of
the vanilla shakes. The study subjects were asked to imagine each
food in great detaila "how it looked and smelled and what it felt
like to eata "and to report any cravings they were having.

Not surprisingly, the people fed only vanilla shakes reported
significantly more cravings than did participants who'd had no diet
restrictions. When the researchers examined the fMRI images generated
by patients with food cravings, they found activation of the
hippocampus, the insula, and the caudate, which are the same brain
areas that other researchers had pinpointed in drug cravings and the
reinforcement of addictive habits.

"This is consistent with the idea that cravings of all kindsa
"whether for food, drugs, or designer shoesa "have common
mechanisms," says Pelchat.

Pure Pleasure

With so many enticements surrounding people every day, how does
someone become addicted to food rather than alcohol, drugs, gambling,
video games, or various other alluring pleasures? A 2002 study by
Gene-Jack Wang and his colleagues at Brookhaven National Laboratory
in Upton, N.Y., gave researchers food for thought.

Dean MacAdam

For the study, Wang's team recruited 30 healthy volunteersa "10 who
were obese, the rest of normal weight. After having the volunteers
fast for 16 hours, the researchers gave them a sugary solution
containing a trace of a radioactive chemical. Wang and his colleagues
then conducted positron-emission tomography scans on the
participants. This test showed where the brain was using the sugar as
fuel, a measure of brain activity.

Right away, Wang says, his team noticed a stark difference between
the brain scans of many of the obese and nonobese volunteers.
Specific areas of the parietal cortex, an area that takes in sensory
information from the body, lit up only in the obese subjects.

Wang checked an anatomy textbook and found that the areas highlighted
in the obese study participants responded to various sensations from
the mouth, lips, and tongue. Studies by other researchers had shown
that these areas aren't overactive in people addicted to drugs.

Wang's team hypothesizes that some obese people get more pleasure
from eating than people of normal weight do. As such, "they may be
more susceptible or vulnerable to some types of food," he says.

Scientists are currently investigating neurological differences
between obese individuals. For example, Wang is employing an
implanted device, called a gastric pacemaker, designed to make the
stomach feel full. The device decreases appetite by stimulating
nerves that control the digestive system. Most obese people eat less
in response to this pacemaker, but some don't respond.

Wang's team hypothesizes that these people's dopamine systems and
other brain areas motivating them to eat may be overriding the system
that senses satiety.

Want a New Drug?

As more information turns up on how drug addiction and obesity are
neurologically similar, some researchers are using the findings to
craft treatments aimed at both problems. The most logical target
seems to be the dopamine system. However, notes Wise, chemicals that
completely block dopamine are "too blunt a tool."

"If you block all dopamine, it blunts all the pleasures of life. We
need to make just a small adjustment to [patients'] lives, like
technicians fine-tune the ratio of fuel and oxygen in a racecar," he says.

Many researchers are therefore targeting brain systems that have some
sway over the system regulated by dopamine. An experimental drug
called rimonabant appears promising. It works by dampening activity
in the endocannabinoid system, a brain network that indirectly hikes
dopamine concentrations in the brain.

In the most recent study of rimonabant's performance, published in
the April 16 Lancet, researchers tested the drug in people who were
overweight or obese. They gave 1,507 volunteers various doses of the
drug or a placebo for 1 year. Of the 599 people on the highest dosea
"20 milligrams (mg)a "of rimonabant, almost 70 percent lost at least
5 percent of their body weight. Only about 50 percent of the
volunteers taking a placebo lost that much weight.

In March 2004 at the American College of Cardiology Scientific
Sessions in New Orleans, researchers announced positive, although
modest, results in a study using rimonabant for smoking cessation. Of
the people who received a 20-mg dose of the drug, about a third quit
smoking within 15 days. Only about one-fifth of the placebo takers
quit in the same time period.

However, another result may give hope to weight-conscious smokers.
People getting 20 mg of rimonabant lost 0.5 pound, on average,
according to Julissa Viana of Sanofi-Aventis, the company that makes
rimonabant and sponsored the study. People who got the placebo gained
about 2.4 pounds.

Wise notes that rimonabant is probably only the first of many drugs
intended to fight both obesity and drug addiction. But until such
drugs are available for prescription, many researchers suggest
following the same tenets that have helped Neal battle his overeating
for the past 15 years: Eat right, exercise, and get a little help
from your friends.

References:

Pelchat, M.L., et al. 2004. Images of desire: Food-craving activation
during fMRI. NeuroImage 23(December):1486-1493. Abstract available at
http://dx.doi.org/10.1016/j.neuroimage.2004.08.023.

Van Gaal, L.F., et al. 2005. Effects of the cannabinoid-1 receptor
blocker rimonabant on weight reduction and cardiovascular risk
factors in overweight patients: 1-year experience from the RIO-Europe
study. Lancet 365(April 16):1389-1397. Abstract available at
http://dx.doi.org/10.1016/S0140-6736(05)66374-X.

Volkow, N.D., and R.A. Wise. 2005. How can drug addiction help us
understand obesity? Nature Neuroscience 8(May):555-560. Abstract
available at http://dx.doi.org/10.1038/nn1452.

Volkow, N.D., G.-J. Wang, et al. 2002. "Nonhedonic" food motivation
in humans involves dopamine in the dorsal striatum and
methylphenidate amplifies this effect. Synapse 44(June 1):175-180.
Abstract available at http://dx.doi.org/10.1002/syn.10075.

Wang, G.-J., N.D. Volkow, et al. 2004. Exposure to appetitive food
stimuli markedly activates the human brain. Neuroimage
21(April):1790-1797. Abstract available at
http://dx.doi.org/10.1016/j.neuroimage.2003.11.026.

______. 2002. Enhanced resting activity of the oral somatosensory
cortex in obese subjects. NeuroReport 13(July 2):1151-1155. Abstract
available at
http://www.neuroreport.com/pt/re/neuroreport/abstract.00001756-200207020-00016.htm.

______. 2001. Brain dopamine and obesity. Lancet 357(Feb. 3):354-357.
Abstract available at http://dx.doi.org/10.1016/S0140-6736(00)03643-6.

Further Readings:

Di Chiara, G., and A. Imperato. 1988. Drugs abused by humans
preferentially increase synaptic dopamine concentrations in the
mesolimbic system of freely moving rats. Proceedings of the National
Academy of Sciences 85(July 15):5274-5278. Available at
http://www.pnas.org/cgi/reprint/85/14/5274.

Di Marzo, V., M. Bifulco, and L. De Petrocellis. 2004. The
endocannabinoid system and its therapeutic exploitation. Nature
Reviews Drug Discovery 3(September):771-784. Abstract available at
http://dx.doi.org/10.1038/nrd1495.

Garavan, H., et al. 2000. Cue-induced cocaine craving:
Neuroanatomical specificity for drug users and drug stimuli. American
Journal of Psychiatry 157(November):1789-1798. Available at
http://ajp.psychiatryonline.org/cgi/content/full/157/11/1789.

Horvath, T.L. 2003. Endocannabinoids and the regulaton of body fat:
The smoke is clearing. Journal of Clinical Investigation 112(Aug.
1):323-326. Available at http://www.jci.org/cgi/content/full/112/3/323.

Kelley, A.E., and K.C. Berridge. 2002. The neuroscience of natural
rewards: Relevance to addictive drugs. Journal of Neuroscience 22(May
1):3306-3311. Available at http://www.jneurosci.org/cgi/content/full/22/9/3306.

MacDonald, A.F., C.J. Billington, and A.S. Levine. 2004. Alterations
in food intake by opioid and dopamine signaling pathways between the
ventral segmental area and the shell of the nucleus accumbens. Brain
Research 1018(Aug. 20):78-85. Abstract available at
http://dx.doi.org/10.1016/j.brainres.2004.05.043.

Pelchat, M.L. 2002. Of human bondage: Food craving, obsession,
compulsion and addiction. Physiology & Behavior 76(July):347-352.
Abstract available at http://dx.doi.org/10.1016/S0031-9384(02)00757-6.

Raloff, J. 2005. Still hungry? Science News 167(April 2):216-220.
Available at http://www.sciencenews.org/articles/20050402/bob9.asp.

Small, D.M., M. Jones-Gotman, and A. Dagher. 2003. Feeding-induced
dopamine release in dorsal striatum correlates with meal pleasantness
ratings in healthy human volunteers. NeuroImage 19(August):1709-1715.
Abstract available at http://dx.doi.org/10.1016/S1053-8119(03)00253-2.

Volkow, N.D., and J.S. Fowler. 2000. Addiction, a disease of
compulsion and drive: Involvement of the orbitofrontal cortex.
Cerebral Cortex 10(March):318-325. Available at
http://cercor.oxfordjournals.org/cgi/content/full/10/3/318.

Volkow, N.D., J.S. Fowler, and G.J. Wang. 2003. The addicted human
brain: Insights from imaging studies. Journal of Clinical
Investigation 111(May 15):1444-1451. Available at
http://www.jci.org/cgi/content/full/111/10/1444.

Volkow, N.D., et al. 2004. Dopamine in drug abuse and addiction:
Results from imaging studies and treatment implications. Molecular
Psychiatry 9(June):557-569. Abstract available at
http://dx.doi.org/10.1038/sj.mp.4001507.

Volkow, N.D., et al. 2002. Role of dopamine, the frontal cortex and
memory circuits in drug addiction: Insight from imaging studies.
Neurobiology of Learning and Memory 78(November):610-624. Available
at http://www.bnl.gov/medical/Personnel/Goldstein/files/NLM02.pdf.

Wise, R.A., and P.P. Rompre. 1989. Brain dopamine and reward. Annual
Reviews of Psychology 40(January):191-225.

Sources:

Marcia L. Pelchat Monell Chemical Senses Center 3500 Market Street
Philadelphia, PA 19104-3308.

Nora D. Volkow National Institute on Drug Abuse National Institutes
of Health Bethesda, MD 20892

Gene-Jack Wang Medical Department Brookhaven National Laboratory
Upton, NY 11973

Roy A. Wise National Institute on Drug Abuse National Institutes of
Health Bethesda, MD 20892