Involvement of the cyclic AMP-responsive element binding protein gene transcription factor in genetic preference for alcohol drinking behavior.
BACKGROUND
Cyclic adenosine 3',5'-monophosphate (cAMP)-responsive element binding (CREB) protein is a gene transcription factor that can integrate the signals mediated via the cAMP second messenger cascade at the gene expression level, which then controls neuronal functions.


METHODS
To examine if the protein kinase A --> CREB signaling cascade is involved in genetic alcohol drinking preference, different measures of CREB were determined in various brain structures of alcohol-preferring (P) and alcohol-nonpreferring (NP) rats.


RESULTS
We show here that CRE-DNA binding activity is significantly decreased in the amygdala but not in the cortex, hippocampus, or striatum of P rats compared with NP rats. The levels of total CREB and phosphorylated CREB protein in the amygdala are significantly lower in P rats compared with NP rats. On the other hand, levels of the alpha-isoform of the catalytic subunit of protein kinase A protein, and basal as well as cAMP-stimulated protein kinase A activity are similar in the amygdala of both P and NP rats.


CONCLUSIONS
Because P and NP rats are genetically bred for high and low alcohol drinking behavior, respectively, these results suggest the possibility that decreased expression of CREB protein in the amygdala may be associated with the high alcohol drinking behavior of P rats.
Pandey
S C
SC
Department of Psychiatry, College of Medicine, University of Illinois and the VA Chicago Health Care System, 60612, USA. scpandey@uic.edu
Mittal
N
N
Lumeng
L
L
Li
T K
TK
D051698:Activating Transcription Factor 2; D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism*; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D014157:Transcription Factors; D017868:Cyclic AMP-Dependent Protein Kinases