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Blocking selected neurotransmitter activity may decrease alcohol consumption

nt of psychiatry at the University of Illinois at Chicago. "This research suggests that alcohol-preferring mice may have higher levels of NPY-Y5 receptors in the brain. Other research suggests that these mice have lower NPY levels in the brain area involved in reward of alcohol drinking. It is also possible that both lower NPY levels and higher NPY-Y5 receptors in the brain may be associated with the excessive alcohol drinking behaviors of these mice."

This study uses alcohol-preferring mice called C57BL/6 to examine the effects of the NPY-Y5 receptor antagonist L-152,804 on the onset and maintenance of alcohol self-administration.

"Most of the known compounds that target NPY receptors do not cross the blood-brain barrier," said Hodge. "L-152,804, however, is a novel compound that was recently shown to both cross the blood-brain barrier and block NPY-Y5 receptors."

Researchers housed 59 male C57BL/6J mice in standard Plexiglas cages (4 per cage) with food and water always available. Mice were trained to self-administer either alcohol (10% v/v) or water during 16-hour sessions. After four months, the mice were injected systemically with L-152,804 (0, 10, 30 or 60 mg/kg) prior to the sessions.

Results indicate that not only does L-152,804 delay the onset of alcohol self-administration, which is considered an index of relapse potential, but it also seems to reduce the reinforcing, or rewarding, effects of alcohol.

"The process by which drug self-administration behavior becomes repetitive is called positive reinforcement," said Hodge. "It reflects the tendency of all animals, human and non-human, to repeat responses that produce a desired outcome. In general, this process functions to sustain behavior that is essential to the individual or species, such as eating, drinking or reproduction. In this particular case, L-152,804 appeared to block the reinforcing effects of alcohol. When taken together, these results su
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14-Dec-2003


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