Alcohol use disorder (AUD) results from disruption of a number of neural systems underlying motivation, emotion, and cognition. Patients with AUD exhibit not only elevated motivation for alcohol but heightened stress and anxiety, and disruptions in cognitive domains such as decision-making. One system at the intersection of these functions is the central norepinephrine (NE) system. This catecholaminergic neuromodulator, produced by several brainstem nuclei, plays profound roles in a wide range of behaviors and functions, including arousal, attention, and other aspects of cognition, motivation, emotional regulation, and control over basic physiological processes. It has been known for some time that NE has an impact on alcohol seeking and use, but the mechanisms of its influence are still being revealed. This chapter will discuss the influence of NE neuron activation and NE release at alcohol-relevant targets on behaviors and disruptions underlying alcohol motivation and AUD. Potential NE-based pharmacotherapies for AUD treatment will also be discussed. Given the basic properties of NE function, the strong relationship between NE and alcohol use, and the effectiveness of current NE-related treatments, the studies presented here indicate an encouraging direction for the development of precise and efficacious future therapies for AUD.
Keywords: Adrenergic receptors; Allostasis; Dependence; Locus coeruleus; Nucleus tractus solitarius; Reward; Withdrawal.