THIS IS YOUR BRAIN ON DRUGS - OR SUGAR

Studies Show the Power of Addiction

For 23 generations this family has stewed in alcohol- each succeeding
offspring slightly worse than the last. If grand-pa seemed a sot, stumbling
home from some reckless adventure, the grandson makes him look positively
sober.

And the grandson's grandson will be that much more likely to spend his
waking hours with his head in the bottle.

For anyone who ever doubted that addiction Was more than a failure of will,
science presents the Mouse Family. With no more prompting than the direction
of their genes these rodents are born to drink. From the 50th day of life,
they chose between a 10 percent alcohol solution and water. Each generation
chooses greater amounts of alcohol. Today, the members of generation 23
polish off the equivalent of three bottles of wine a day, says Nicholas
Grahame, who runs this research project at the Indiana University School of
Med-icine.

It's simply an inborn, and inbred, pref-erence for the effects of ethanol,
and it's a preference that will help science solve the quandaries of
addiction.

An estimated 10 million Americans are alcoholics. The National Household
Survey on Drug Use estimates 3.6 million Americans depend on illicit drugs.
Another 66 million are tobacco addicts. As high as these numbers are, why
aren't they higher? Far many more of us drink socially. Some 60 percent of
us have experi-mented with illegal drugs. Who knows how many try cigarettes
each year?

Then there is the nature of addiction: Not merely a habit - as addiction
researcher Terry E. Robinson at the University of Michigan says, we do not
sacrifice family, friends, and self-respect to feed our shoe--tying habit-
something else accounts for this compulsion.

Jaak Panksepp traces a complicated map of neurons branching like frantic
tributaries in a drawing of the brain. This is where it all happens. The
shopping sprees. The long nights at the one-armed bandit. The need for a
drug that overtakes everything else.

It is not meant to be your addiction cen-ter, says the Bowling Green state
Univer-sity professor of behavioral neuroscience. It evolved for hunting,
and seeking, and wanting. It is what makes animals forage for food, and
where we learn to do what it takes to survive. It comes to life when it is
time to eat. It sends us out for groceries. It prompts the pursuit of sex.
And it is crucial in addiction.

Why do you think they call it dopamine? Dopamine is the name of the
chemical message -- a neurotransmitter -- that forms the backbone of this
seeking and wanting system. In the course of getting hooked on anything from
alcohol to cig-arettes, to -- a growing number of studies show -- sugar,
dopamine is a major player. It shows up in parts of the brain involved in
emotion processing, decision making. It helps rewire the brain from the
first time we sample an addictive substance, and in some of us, it continues
the redesign, forming brains that are never the same again.

In fact, the number of dopamine recep-tors we are born with probably plays a
role in our risk of addiction. Receptors are the intake ports on nerve cells
designed to receive shipments of neurochemicals. A study published last year
in the journal Synapse by Nora D. Volkow and a team from Brookhaven National
Laboratory in Upton, N.Y., demonstrated that people with a smaller number -
of one type of dopamine receptor -- the D2 receptor- simply enjoyed drugs
more. The fewer receptors, the greater the pleasure. While those with the
most receptors found the stimulant dose unpleasant.

But dopamine is not the only neuro-transmitter with a role in addiction. In
fact, mice genetically engineered to have naturally high dopamine levels
continue to self-administer cocaine, thus over--turning the theory that
there would be no added high from cocaine if dopamine were already abundant.
It was not until researchers also raised serotonin levels that compulsive
drug taking stopped, a study in the Proceedings of the National Academy of
Science demonstrated.

Research shows that the first experience with an addictive drug starts the
brain's redesign.

Although the effects of cocaine, heroin, and cigarettes are distinctly
different, one thing they all do is create craving. Work by Antonello Bonci
of the University of California, San Francisco, shows that this crav-ing
begins in a little pea of brain tissue, deep in the heart of the brain,
called the ventral tegmental region.

It is here where the first blast of cocaine -- or alcohol or nicotine -
begins remaking neural architecture, doubling the respon-siveness of
dopamine neurons. Although the drug sensation may last an hour, the ventral
tegmental region changes for as long as a week, rodent-brain studies show.

Dr. Bonci said this makes dopamine cells more sensitive to calls for more
dopamine.

"There is speculation that this will make a subject more likely to take
cocaine in the near future. You may be opening a window of vulnerability,"
he said.

A study Dr. Bonci and others published February in the journal Neuron showed
that psychoactive drugs that do not cause addiction, such as Prozac, caused
no changes in the ven-tral tegmental area. Yet every addictive drug tested
thus far sensitizes these neurons.

Continued drug use recruits more areas of the brain for neurochemical
sensitization. Neuron structures change, not only in the midbrain, which
rules emotional memory and plays a role in decision making, but also in the
region where we con-duct our most sophisticated reasoning: the prefrontal
cor-tex, right behind the forehead.

Researchers note that changes seen in cocaine addiction resemble the
architecture of obsessive-compulsive disorder.

Many Addictions appear to trigger a decrease in one type of dopamine
transporter. A transporter allows neurons that release a neurochemical to
suck it back up again. The fewer transporters available, the longer dopamine
can stimulate adjoining neurons. Researchers at Brookhaven examined 15
people who used methamphetamines five days a week for two years. Twenty-four
percent of their dopamine transporters were gone. Normal aging would take 40
years to reduce transporters to that level. Although transporter numbers
returned to almost normal after 14 months of abstinence, the subjects did
not recover lost fine-motor skills or memory.

Growing knowledge about these brain changes suggests that drugs are not the
only things one becomes addicted to. Some foods can trigger the same, or
similar, profound, neurochemically driven, compulsion. Bartley. G. Hoebel,
a researcher at Princeton Univer-sity in New. Jersey, said his research
shows sugar becomes addictive when rats binge on it. The implication is that
sugar might be just as addictive when some humans binge.

Researchers in his lab trained rats to binge on sugar by enforcing 12-hour
fasts that, covered the rats' heaviest feeding time. To break the fast, rats
received sugar water and food. This regimen continued for a month before
sugar was denied. The rats shook like junkies. Their teeth chattered. They
fanned their paws and shook their heads. Symptoms were even sharper when
researchers gave rats a drug called naloxone to induce with-drawal. Naloxone
triggers heroin withdrawal, and it apparently works on sugar as well. But
when the rats got mor-phine or sugar, withdrawal symptoms abated.

"There are lots of overlaps that show eating and drug abuse influence the
same neural system," Dr. Hoebel said. "We've shown, for example, food
deprivation lowers dopamine release... so the dopamine system seems to be
involved in both body weight regulation and drug abuse."

Research at Brookhaven dem-onstrated the food-dopamine connection by
revealing that obese individuals released dopamine with just the sight and
smell of food. Increased dopamine accompanied increased craving. Gene-Jack
Wang, clinical director of the Positron Emission ,Tomography Imaging Group.
at Brookhaven, conducted the study. His earlier work made a convincing link
between obesity and addiction.

"We published an article in Lancet in 2001 that showed obese people have
fewer dopamine D2 receptors. It's very similar to those in drug addicts. So
we asked ourselves, how did that happen? Why does dopamine have anything to
do with obesity?" Dr. Wang said.

In fact, the Lancet study showed that the higher a per-son's body mass
index, the lower his level of dopamine receptors. If there is any good news
here, it is that exercise increases the number of dopamine D2 receptors.

Dopamine could play a role in yo-yo dieting, the way it appears to be
involved in drug relapse. For instance, rats forced to lose weight saw a
drop in dopamine levels, as do addicts who abstain from drugs.

Further cementing the addic-tive power of sugar, Dr. Hoebel showed in a
study published last year in Pharmacology, Bio-chemistry, and Behavior, that
animals sensitized to cocaine will respond the same way to sugar, a
phenomenon called cross-sensitization. Typically, cross-sensitization
applies to two drugs in the same class: for instance, those addicted to
amphetamines respond the same way to cocaine. Cocaine addicts respond to
alcohol, and so on. Amphetamine-addicted rats in Dr. Hoebel's work responded
.the same way to sugar and drank more sugar water than rats not drug
sensi-tized.

None of this is particularly odd, when one considers that our survival
demands that at, our earliest moments in life, we need compulsions to keep
us alive. Dr. Hobel suggests, in fact, that our first addiction, and our
healthiest, may be to mother's milk. Our lives require an addiction
mechanism. Unfortunately for some, drugs of abuse - and even some food -
hijacks an intricately designed life system to other ends entirely.