DON'T GET USED TO IT

You Might Not Need To Take Ever More Opiates To Get The Same Effect

IT MAY be possible to get morphine's painkilling effects without
having to take ever larger doses-and, possibly, without risking
withdrawal symptoms. The finding turns conventional theories on their
head.

Morphine kills pain by mimicking the body's natural opiates, binding
to special ised receptors on nerve cells. When natural opiates bind
to them, the receptors are sucked inside the cell--a process called
enclocytosis--and then return to the cell surface. But when morphine
binds to the receptors, it blocks endocytosis.

This was thought to prolong morphine's effect and give it its power.
"It seemed like the last thing you'd want to do to is trigger
endocytosis," says Jennifer Whistler of the University of California,
San Francisco.

Whistler's team set out to test this theory when they discovered that
a protein called DAMGO could trigger endocytosis of morphine-bound
receptors. They used a standard pain test in which a laser is focused
on the tail of rats. The rats normally flick their tails away in
about two seconds.

Rats given morphine didn't flick their tails for six seconds. But the
effects soon wore off. After four days on the same dose, the animals
flinched after just two seconds.

But when the researchers added a tiny trace of DAMGO to the morphine,
the results were dramatic. Even after a week, the animals' response
hardly changed at all. By itself, though, DAMGO had no effect.

DAMGO can't be used to treat people-it is too large to enter the
brain-but Whistler thinks drugs with the same effect could be found.
The findings also have implications for related opiates such as
heroin. Could junkies get more bang for their buck with such a
booster, for example?

Glen Hanson of the US National Insti-tute on Drug Abuse isn't sure.
Painkilling is different to the high such drugs create, he says. And
whether endocytosis affects withdrawal and addiction isn't yet clear.
"This raises a lot of exciting issues, " he says. "There are going to
be a ton of phenomena to examine."