Review — In vivo electrochemical measurements of norepinephrine in the brain: Current status and remaining challenges

Norepinephrine (NE), one of the major catecholamines in the brain, is involved in many physiological and behavioral processes such as stress and reward. Despite its important roles, NE remains largely unexplored compared to the other major central catecholamine, dopamine (DA). This is due in part to the diffuse distribution of NE projections throughout the brain and accessibility of NE neurons, complicating detection of the relatively low physiological NE concentrations. Recent studies have demonstrated that in vivo fast-scan cyclic voltammetry coupled with carbon-fiber microelectrodes can detect real time, subsecond changes of NE in the brains of both anesthetized and awake-behaving rats, offering a local view of NE regulation (release and clearance). Furthermore, these studies have revealed different regulatory mechanisms between NE and DA, and that these two catecholamines have functional differences as well. For the last decade, these fundamental studies provided new insights into the understudied roles of NE in reward/aversion processes, drug addiction, and related behavioral responses. However, there are still limitations in the electroanalytical determination of NE in vivo in terms of selectivity. Here, the current status of electrochemical measurements of NE and associated findings are highlighted, and remaining challenges are discussed.