Anxiety and alcohol abuse disorders: a common role for CREB and its target, the neuropeptide Y gene

Abstract

It has been hypothesized that anxiety disorders play an important role in the initiation and maintenance of alcohol drinking behaviors. However, the molecular mechanisms for the association between anxiety and alcohol abuse are not well understood. Structures of the extended amygdala, particularly the central nucleus of amygdala, are involved in anxiety and in motivational aspects of alcohol drinking behaviors. Here, I propose that cAMP response element-binding protein (CREB) has a role in anxiety and alcohol drinking behaviors. The CREB gene transcription factor regulates the expression of the gene encoding neuropeptide Y (NPY), and decreased concentrations of NPY are implicated in anxiety and alcohol drinking behaviors. Therefore, decreased function of CREB in the central nucleus of the amygdala might regulate anxiety and alcohol intake via decreased expression of NPY, and might provide a common link between anxiety and alcohol abuse disorders. I also suggest that, via CREB, NPY might interact with other CREB target genes, such as the gene encoding brain-derived neurotrophic factor, and that this CREB-mediated interaction might be important in the regulation of anxiety and alcohol drinking behaviors.