Central Noradrenergic Interactions with Alcohol and Regulation of Alcohol-Related Behaviors

Abstract

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.

The Influence of Moderate Physical Activity on Brain Monoaminergic Responses to Binge-Patterned Alcohol Ingestion in Female Mice

“…Growing evidence suggests that increases or decreases of brain region-specific noradrenergic signaling are common responses to drugs of abuse, including alcohol (Fitzgerald, 2013 ; Koob and Volkow, 2016 ). However, mixed results have been found concerning NE concentrations following acute alcohol exposure in rodent models (Vazey et al, 2018 ). Moreover, research into the potential alcohol-induced changes to NE in the prefrontal cortex or striatum that have been linked to behavioral or neurophysiological outcomes is limited (Vazey et al, 2018 ).…”

“…However, mixed results have been found concerning NE concentrations following acute alcohol exposure in rodent models (Vazey et al, 2018 ). Moreover, research into the potential alcohol-induced changes to NE in the prefrontal cortex or striatum that have been linked to behavioral or neurophysiological outcomes is limited (Vazey et al, 2018 ). Some evidence suggests that alcohol’s rewarding properties may depend on heightened NE levels in the prefrontal cortex (Ventura et al, 2006 ).…”

“…Moreover, alcohol access during DID had a relatively subtle influence on NE concentrations across brain areas. This is interesting because NE has been another focal point of past work investigating the acute and chronic effects of alcohol abuse (Koob and Kreek, 2007 ; Fitzgerald, 2013 ; Vazey et al, 2018 ). The reasons for distinctions between the current and past findings are not entirely clear.…”

“…The reasons for distinctions between the current and past findings are not entirely clear. However, both the noradrenergic system and prefrontal cortex are key components of the stress response, which is more likely to be evoked during forced ethanol exposure (Koob, 2014 ; Vazey et al, 2018 ). Moreover, while mice ingested ethanol at levels comparable to the National Institute on Alcohol Abuse and Alcoholism standard for binge drinking (see Figure 2 ), studies employing techniques like gavage or i.p.…”

Biobehavioral Interactions Between Stress and Alcohol

“…In another study of rats, blockade of norepinephrine signaling during withdrawal attenuated alcohol drinking 68. See the review by Vazey and colleagues74 for further discussion of this topic.…”