The neurobiology of alcohol craving and relapse

Abstract

A major block to recovery from alcoholism is substantial alcohol craving and the chronic relapsing nature of the illness. This chapter reviews relevant structural and functional neuroimaging studies and discusses neural mechanisms underlying alcohol craving and relapse in the context of influential risk factors (i.e., alcohol, alcohol cue, and stress). Review of neuroimaging studies suggests that neuroadaptations in the cortico-striatal-limbic circuit encompassing the medial prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, striatum, and amygdala significantly contribute to overwhelming alcohol craving and early relapse after a period of abstinence. The cortico-striatal-limbic circuit plays an important role in the modulation of emotion, reward, and decision making. As functional and structural chronic alcohol-related neuroadaptations are consistently reported in this circuit, it is likely that sensitization of this circuit from continued alcohol abuse may contribute to high alcohol craving and early relapse via impairments in the prefrontal executive function related to emotion regulation and decision making. This vulnerable neurobiologic state may be manifested as compulsive craving and intense urge to resume alcohol drinking in the face of environmental risk factors, including alcohol, alcohol cue, or stressful live events.

Introduction

A major problem jeopardizing recovery from alcoholism is high alcohol craving and the chronic, relapsing nature of the illness. Many individuals with alcohol use disorders (AUD) report significant difficulties with craving and struggle with relapse urges (Fox et al., 2007, Breese et al., 2011). Researchers have also identified that alcohol craving and relapse are critical factors perpetuating the malady of chronic alcoholism (Bottlender and Soyka, 2004, Sinha et al., 2011) and thus, mechanisms underlying alcohol craving and relapse have been a central focus of alcohol research, including in neuroimaging studies.

Neuronal processes underlying alcohol craving and relapse are complex due to an interplay between neuroadaptations from chronic alcohol abuse and environmental risk factors affecting the developmental course of alcoholism. After a prolonged period of alcohol abuse, neuroadaptations from repeated alcohol consumption increase allostatic load on key neural circuit of emotion and reward regulation (Breese et al., 2011, Seo and Sinha, 2011, Seo et al., 2013) and place AUD individuals in an emotionally susceptible state. In the face of emotional or alcohol-related challenges (e.g., stress and alcohol cues), vulnerable AUD individuals often lose control over alcohol craving and make poor decisions, thereby increasing relapse risk (Bechara et al., 2001, Goldstein et al., 2009, Sinha, 2012, Sinha, 2013). Thus, to have a comprehensive understanding of neural mechanisms underlying craving and relapse, relevant brain functions should be considered in the context of neuroadaptations and interactions with environmental risk factors.

This chapter is intended to provide a neurobiologic understanding of brain structures and functions related to alcohol craving and relapse risk. It will review relevant neuroimaging studies and discuss neural mechanisms underlying craving and relapse as well as significant risk factors in the course of chronic alcoholism. The first section provides a review of the role of neuroadaptations in chronic alcoholism. In the second section, we review the basic concepts and role of alcohol craving and relapse in the course of alcoholism. In the third section, functional brain changes associated with alcohol craving and relapse will be reviewed in the context of environmental risk factors such as alcohol, alcohol-associated cues, and stress. In this section, the emphasis is on the functional mechanisms related to emotion regulation and decision making in the prefrontal-striatal-limbic circuit and their contributions to alcohol craving and relapse. The final section concludes the review and discusses future research directions. Elucidating the neural mechanisms underlying alcohol craving and relapse in the context of its risk factors will help understand complex vulnerability factors for alcohol-related pathology and could facilitate the development of effective treatments.