The application is a third submission of a CDA-2 that has been reviewed by a VA review panel twice before. The previous application was reviewed favorably with the majority of the negative comments being related to the mentoring program. In addition, there were some small comments related to the specificity of the effect and the region of the brain to be studied and the use of pharmacological inhibitors. The author has responded very strongly scientifically by adding figures 8 and 14 to the revised proposal where she shows that ethanol intake is significantly decreased in the AC1 inhibitor group. I think this is a thorough response to the scientific portion. Regarding mentoring, the applicant has provided more information regarding the productivity, seniority and the training to be provided by Dr. Conti. In my opinion, this response was less convincing. My overall level of enthusiasm is only moderate.
Our veterans face a disproportionately increased risk to develop alcohol use disorders, resulting in a significant physical, emotional and financial impact. Although therapies exist to alleviate alcohol dependence, clinical evidence indicates that a proportion of individuals, particularly within the afflicted veteran population, do not adequately respond to these treatments. The proposed project seeks to identify the novel role of specific enzymes, adenylyl cyclases, in regulating signaling pathways that confer neuronal adaptations to alcohol in brain reward circuits. Thus, this project aims to address the critical need for an advanced understanding of the mechanisms underlying maladaptive plasticity in the addicted brain. Likewise, it upholds the mission for VA patient care and rehabilitation by providing a structural framework to develop therapeutic strategies that have the potential to improve/expand the effective treatment options for individuals suffering from alcohol use disorders.