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Review
. 2005 Oct;115(10):2697-9.
doi: 10.1172/JCI26436.

The anxious amygdala: CREB signaling and predisposition to anxiety and alcoholism

Gary Wand  1
Affiliations
Review

The anxious amygdala: CREB signaling and predisposition to anxiety and alcoholism

Gary Wand. J Clin Invest. 2005 Oct.

Abstract

The amygdala is believed to play a key role in assigning emotional significance to specific sensory input, and conditions such as anxiety, autism, stress, and phobias are thought to be linked to its abnormal function. Growing evidence has also implicated the amygdala in mediation of the stress-dampening properties of alcohol. In this issue of the JCI, Pandey and colleagues identify a central amygdaloid signaling pathway involved in anxiety-like and alcohol-drinking behaviors in rats. They report that decreased phosphorylation of cAMP responsive element-binding protein (CREB) resulted in decreased neuropeptide Y (NPY) expression in the central amygdala of alcohol-preferring rats, causing high anxiety-like behavior. Alcohol intake by these animals was shown to increase PKA-dependent CREB phosphorylation and thereby NPY expression, subsequently ameliorating anxiety-like behavior. These provocative data suggest that a CREB-dependent neuromechanism underlies high anxiety-like and excessive alcohol-drinking behavior.

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Figures

Figure 1
Figure 1
The amygdala and cAMP-dependent signaling. Located in the temporal lobe and forming part of the limbic system, the amygdala processes and then assigns emotional importance to specific sensory input. The amygdala has also been implicated in the generation of anxiety-like behaviors as well as mediation of the stress-dampening affects of alcohol. In this issue of the JCI, Pandey et al. (13) show that alcohol intake activated PKA signaling, resulting in increased phosphorylation of CREB and increased NPY expression in the CeA of P rats. These neurochemical changes were accompanied by decreased anxiety-like behavior. Not only were these observations mimicked by using a cAMP analog to activate PKA signaling, but alcohol self-administration in these rats was also reduced. To ensure proof of principle, the investigators infused a PKA inhibitor into the CeA of NP rats. In contrast to the results observed in P rats, the infusion provoked anxiety-like behaviors and increased alcohol intake. It appears that a CREB-dependent neuromechanism within the CeA may modulate anxiety-like behavior and alcohol intake. The findings provide a genetic model to understand how a neural substrate creates anxiety, which results in alcohol consumption to reverse a state of negative affect. The observations also open up new avenues in which to pursue pharmacological manipulation of CREB and/or NPY expression in order to modify heavy alcohol intake.
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