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Involvement of the Cyclic AMP‐Responsive Element Binding Protein Gene Transcription Factor in Genetic Preference for Alcohol Drinking Behavior
Author(s) -
Pandey Subhash C.,
Mittal Navdha,
Lumeng Lawrence,
Li TingKai
Publication year - 1999
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1999.tb04663.x
Subject(s) - creb , protein kinase a , amygdala , cyclic amp response element binding protein , endocrinology , medicine , cyclic adenosine monophosphate , creb1 , striatum , biology , response element , transcription factor , chemistry , gene expression , microbiology and biotechnology , kinase , gene , promoter , biochemistry , receptor , dopamine
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 α‐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.