Enzyme Might Be Target for Treating Smoking,
Alcoholism at Same Time
Source: UCSF press release
Date: September 12, 2011
An enzyme that appears to play a role in controlling
the brain's response to nicotine and alcohol in mice
might be a promising target for a drug that
simultaneously would treat nicotine addiction and
alcohol abuse in people, according to a study by
researchers at the Ernest Gallo Clinic and Research
Center, affiliated with the University of California,
San Francisco.
Over the course of four weeks, mice genetically
engineered to lack the gene for protein kinase C (PKC)
epsilon consumed less of a nicotine-containing water
solution than normal mice, and were less likely to
return to a chamber in which they had been given
nicotine.
Robert O. Messing, MD
In contrast, normal mice steadily increased their
consumption of nicotine solution while the mice lacking
PKC epsilon did not.
The study was conducted by Gallo senior associate
director and investigator Robert O. Messing, MD, UCSF
professor of neurology, and Gallo researcher Anna M.
Lee, PhD.
In normal mice, as in humans, nicotine binds to a
certain class of nicotinic receptors located on
dopamine neurons, which causes dopamine to be released
in the brain. Dopamine creates a feeling of enjoyment,
and thus prompts a sense of reward. Lee and Messing
found that mice lacking PKC epsilon are deficient in
these nicotinic receptors.
The study appears in the online Early Edition of the
Proceedings of the National Academy of
Sciences for the week of September 12, 2011.
The finding complements earlier research in which
Messing found that mice genetically engineered to lack
the PKC epsilon enzyme drank less alcohol than normal
mice and were disinclined to return to a chamber in
which they had been given alcohol.
“This could mean that these mice might not get the
same sense of reward from nicotine or alcohol,” said
Messing. “The enzyme looks like it regulates the part
of the reward system that involves these nicotinic
receptors.” The reward system is a complex of areas
in the brain that affect craving for nicotine, alcohol
and other addictive substances.
The next step in the research, said Messing, would
be to develop compounds that inhibit PKC epsilon. The
ultimate goal, he said, would be medications that could
be used “to take the edge off of addiction by helping
people get over some of their reward craving.”
The research was supported by grants from the U.S.
Public Health Service and the Canadian Institute of
Health Research, and by funds provided by the State of
California for medical research on alcohol and
substance abuse through UCSF.
The UCSF-affiliated Ernest Gallo Clinic and Research
Center is one of the world’s preeminent academic
centers for the study of the biological basis of
alcohol and substance use disorders. Gallo Center
discoveries of potential molecular targets for the
development of therapeutic medications are extended
through preclinical and proof-of-concept clinical
studies.
UCSF is a leading university dedicated to promoting
health worldwide through advanced biomedical research,
graduate-level education in the life sciences and
health professions, and excellence in patient care.
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