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Scripps Research scientists find key mechanism in transition to alcohol dependence
Date:5/31/2011

and colleagues observed the effects of the administration neuropeptide Y in the central amygdala on alcohol drinking in rats. Alcohol-dependent rats were allowed to press levers for ethanol and water during daily withdrawal from chronic alcohol exposure.

"Normally, the transition to alcohol dependence is accompanied by gradually escalating levels of alcohol consumption during daily withdrawals," Gilpin explained. "The aim of this protocol was to examine whether neuropeptide Y infusions during daily withdrawals would block this escalation of alcohol drinking."

The scientists report a suppression of alcohol consumption with chronic neuropeptide Y infusions and detailed some of the neurocircuitry involved. Ethanol normally produces robust increases in inhibitory GABAergic transmissionGABA is another neurotransmitterin the central amygdala, but this effect is blocked and reversed by neuropeptide Y.

Gilpin notes the scientists were surprised at one aspect of the findingsthe role of a subset of neuropeptide Y receptors known as Y2 receptors. "Previous behavioral evidence suggested that antagonism of Y2 receptors in whole brain suppresses alcohol drinking, similar to the effects of neuropeptide Y," he said. "However, our data suggest that Y2 receptor blockade in central amygdala might actually increase alcohol drinking, presumably by affecting pre-synaptic release of GABA. These data also suggest that antagonism of post-synaptic Y1 receptors in central amygdala provides a viable pharmacotherapeutic strategy, a hypothesis supported by previous work from other labs."

Two additional aspects of the findings are worth noting, Roberto says. First, repeated neuropeptide Y administration not only blocked the development of excessive alcohol consumption in dependent rats, but also tempered the moderate increase in alcohol consumption following periods of abstinence in non-dependent rats. Second, neuropeptide Y exhibited long-term efficacy in su
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

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