As is evident from the preceding sections, a fundamental basis of knowledge exists for the changes to EC system function over the development of ethanol dependence, but much work needs to be done to establish a mechanism for how these changes contribute to addiction pathology. In particular, studies employing region specific modulation of EC signaling are needed to establish the brain nuclei important for EC-mediated contributions to the various phases of alcohol dependence, including: the escalation of use, the negative affect and stress associated with withdrawal, and the reinstatement to drug-seeking following abstinence. Beyond establishing the mechanistic contributions of the EC in the development of alcohol dependence, there are additional areas of EC research that may prove fruitful in our understanding of addiction. Some of these topics have recently emerged as our knowledge of the basic molecular components of the EC system continues to grow, and others involve complex experimental designs that are appropriate only now that a fundamental understanding of the alterations to EC signaling in alcohol dependence is in hand. This section of the review will seek to provide a list of these burgeoning issues along with research relevant to their potential role in AUDs.
