Background
During the transition to alcohol and drug addiction, neuromodulator systems in the
extended amygdala are recruited to mediate aspects of withdrawal and relapse via convergence
on inhibitory gamma-aminobutyric acid (GABA) neurons in central amygdala (CeA).
Methods
This study investigated the role of neuropeptide Y (NPY) in excessive alcohol drinking
by making rats dependent on alcohol via alcohol vapor inhalation. This study also
utilized intracellular and whole-cell recording techniques to determine the effects
of NPY on GABAergic inhibitory transmission in CeA, synaptic mechanisms involved in
these NPY effects, and NPY interactions with alcohol in the CeA of alcohol-naive and
alcohol-dependent rats.
Results
Chronic NPY treatment blocked excessive operant alcohol-reinforced responding associated
with alcohol dependence, as well as gradual increases in alcohol responding by intermittently
tested nondependent control animals. Neuropeptide Y decreased baseline GABAergic transmission
and reversed alcohol-induced enhancement of inhibitory transmission in CeA by suppressing
GABA release via actions at presynaptic Y2 receptors.
Conclusions
These results highlight NPY modulation of GABAergic signaling in central amygdala
as a promising pharmacotherapeutic target for the treatment of alcoholism. Gamma-aminobutyric
acid neurons in the CeA likely constitute a major point of convergence for neuromodulator
systems recruited during the transition to alcohol dependence.
Key Words
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Article info
Publication history
Published online: April 04, 2011
Accepted:
February 7,
2011
Received in revised form:
February 4,
2011
Received:
November 29,
2010
Identification
Copyright
© 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
