Article

Effects of PKA modulation on the expression of neuropeptide Y in rat amygdaloid structures during ethanol withdrawal.

Department of Psychiatry, The Psychiatric Institute, University of Illinois, Chicago, IL 60612, USA.
Peptides (impact factor: 2.43). 10/2003; 24(9):1397-402. DOI:10.1016/j.peptides.2003.08.008 pp.1397-402
Source: PubMed

ABSTRACT We recently reported that neuropeptide Y (NPY) protein levels and cAMP responsive element binding (CREB) protein phosphorylation are lower in amygdaloid structures during ethanol withdrawal after chronic exposure. Furthermore, we reported that normalization of CREB phosphorylation by infusing protein kinase A (PKA) activator into the central amygdala prevents anxiety-like effects in rats during ethanol withdrawal. Here we investigated whether normalization of CREB phosphorylation by infusing PKA activator (Sp-cAMP) into the central amygdala also normalizes the expression of NPY during ethanol withdrawal. Sprague-Dawley male rats were cannulated targeting the central amygdala and then treated either with Lieber-DeCarli ethanol diet or control diet for 15 days. Subsequently ethanol-fed rats were withdrawn for 0 and 24h. The control-diet fed and ethanol-withdrawn rats were infused twice with PKA activator or inhibitor (Rp-cAMP). The protein and mRNA levels of NPY were determined in amygdaloid structures using gold-immunolabeling and the in situ RT-PCR procedure. It was found that chronic ethanol treatment has no effect on mRNA and protein levels of NPY in the central, medial, or basolateral amygdala. On the other hand, ethanol withdrawal produced significant reductions in mRNA and protein levels of NPY in the central and medial but not in the basolateral amygdala. The reductions in mRNA and protein levels of NPY were normalized in the central amygdala by infusion with PKA activator in ethanol-withdrawn rats. On the other hand, PKA-inhibitor infusion does not have any effect on mRNA and protein levels of NPY in the central amygdala of ethanol-withdrawn rats, but significantly decreased the expression of NPY in the central amygdala of control-diet fed rats. These results suggest that the decreased cellular expression of NPY in the central amygdala may play an important role in the CREB-mediated regulation of anxiety-like behaviors during ethanol withdrawal.

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Keywords

amygdaloid structures
 
anxiety-like effects
 
basolateral amygdala
 
cAMP responsive element binding
 
central amygdala
 
chronic ethanol treatment
 
control diet
 
CREB phosphorylation
 
CREB-mediated regulation
 
decreased cellular expression
 
ethanol withdrawal
 
ethanol-fed rats
 
ethanol-withdrawn rats
 
infusing PKA activator
 
infusing protein kinase
 
Lieber-DeCarli ethanol diet
 
PKA activator
 
PKA-inhibitor infusion
 
situ RT-PCR procedure
 
Sprague-Dawley male rats
 

Huaibo Zhang