Brain Receptor May Be Key to Non-Addictive Morphine

vector6 at vector6 at
Wed Jul 31 14:11:04 EDT 2002

Brain Receptor May Be Key to Non-Addictive Morphine
Tue Jul 30, 5:30 PM ET

NEW YORK (Reuters Health) - Blocking a particular brain
receptor may minimize the addictive nature of morphine
without diminishing the drug's pain-killing effects,
new research suggests.

Morphine is widely used to treat severe pain, but one
of its drawbacks is that patients can become addicted
to the drug. A structure in the brain called the M5
muscarinic acetylcholine receptor is a component of the
brain system involved in the pleasurable effects of
morphine. Researchers set out to see whether blocking
the receptor would minimize the risk of morphine

The investigators first genetically engineered mice to
deactivate the gene for the M5 receptor. Switching off
the M5 receptor substantially reduced the desire for
morphine in these mice.

When normal mice were given morphine, the animals,
presumably in search of another fix, spent extra time
hanging around the part of the cage where they had
received the drug. In contrast, mice that had the
receptor turned off did not linger in this part of the
cage unless they were given a very high dose of the

Dr. Anthony S. Basile, formerly of the National
Institute of Diabetes and Digestive and Kidney Diseases
in Bethesda, Maryland, is the lead author of a report
on the findings published in the Early Edition of the
Proceedings of the National Academy of Sciences ( news
- web sites). Basile is now at Alkermes, Inc. in
Cambridge, Massachusetts.

The researchers wanted to make sure that blocking the
receptor did not affect the pain-killing powers of
morphine. Even though switching off the receptor seemed
to make morphine less addictive, the engineered mice
experienced the same level of pain relief as normal
mice, the report indicates. And the investigators also
found that the genetically engineered mice experienced
fewer withdrawal symptoms after being taken off

The findings suggest that a drug that blocks the M5
receptor may be an effective way to reduce the risk of
addiction to morphine without sacrificing pain relief,
according to Basile and his colleagues. They note that
the receptor is present mainly in the brain, so a drug
that blocks the receptor is unlikely to cause serious
side effects.

Because nicotine, alcohol, cocaine and other drugs all
affect similar brain circuitry as morphine, the M5
receptor may also be involved in other types of
addiction, the researchers report.

Eli Lilly Research Laboratories provided some of the
funding for the research.

SOURCE: Proceedings of the National Academy of Sciences

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