Project Summary (Abstract) Addiction is a chronic relapsing disorder characterized by compulsive drug-seeking which persists despite adverse consequences [WHO 1992; American Psychiatric Association 2013]. in the past few years, misuse of opioids (both prescribed and illegal) increased considerably. However, there are very few effective and approved pharmacotherapies available [Pierce et al. 2012]. Recent research activities in the field of orexin biology have demonstrated the significance of these receptors in the domain of addiction. The development of a PET imaging tracer would permit detection and quantification of orexin receptors in vivo thereby accelerating research and increasing our understanding of orexin functions in the domain of drug addiction. The specific aims of this project, will focus on the synthesis, evaluation and characterization of potential OX1R antagonists (Aim 1). Perform In vivo quantification of the binding potential (BP) of the candidate OX1R radiotracer in baboons (Aim 2). If successful, this project will provide “proof of concept” imaging data and a lead PET imaging tracer that can be further examined in human as part of a future R01 application.

Project Narrative The orexin system is an attractive potential therapeutic target that demonstrated its involvement in drug addiction. The development of a novel radioligand for PET imaging targeting orexin 1 receptor would be useful in order to quantify the orexin 1 receptors in vivo.