(Invited) In Vivo Electroanalytical Measurements of Norepinephrine in the Brain: Current Status and Remaining Challenges

Abstract

Norepinephrine (NE), one of the major catecholamines in the brain, is involved in many physiological processes and behaviors ranging from fear and anxiety to reward. Despite its important roles, NE has largely been unexplored compared to the other central catecholamine, dopamine (DA). This is due in part to the diffuse distribution of NE projections throughout the brain and challenges of its low physiological concentration and anatomy, complicating its detection. Specifically, NE is ordinarily one to two orders of magnitude lower in concentration than that of DA and many rodent brain regions that have appreciable amounts of NE are only a few hundred microns across. Recent studies have demonstrated that fast-scan cyclic voltammetry (FSCV) coupled with carbon-fiber microelectrodes enables the detection of subsecond changes of NE in the brain of anesthetized and awake behaving rats in real time, offering a local view of NE regulation (release and clearance). Although the regulatory mechanisms of NE and DA neurotransmission have many similarities, these studies have revealed that NE has important functional differences compared to DA. These results have provided new insights into the understudied role of NE in reward/aversion processes and drug abuse, and their related behavioral responses for the last decade. However, there are still limitations in the electroanalytical determination of NE in vivo in terms of selectivity and sensitivity. Here, the current state of electrochemical measurements of NE and associated findings are highlighted and the remaining challenges are discussed.