**Alcohol Cues, Craving, and Relapse: Insights from Animal Models**

Melanie M. Pina and Amy R. Williams

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/63105

#### **Abstract**

Alcoholism is a chronic relapsing and remitting disorder, where relapse to drinking is often triggered by an intense desire for alcohol (craving) and the consequent motiva‐ tion to obtain alcohol (seeking). Environmental stimuli (cues) associated with past alcohol use are believed to strongly contribute to relapse, as exposure to these cues can trigger intense feelings of craving and drive alcohol seeking. Over the past several decades, much progress has been made in identifying the neurobiological correlates of alcohol seeking and relapse. Much of this progress is owed to the development of animal models and advanced techniques to manipulate neural activity. In this chapter, we describe some of the most commonly used rodent models of alcohol intake and seeking as well as the methods used to identify the neural structures and circuits involved in alcohol-mediat‐ ed behavior. Several of the most routinely identified brain structures in alcohol seeking are also described.

**Keywords:** alcohol, ethanol, relapse, amygdala, accumbens, VTA

## **1. Introduction**

Alcohol use disorders (AUDs) constitute a major global health concern. In 2013 alone, 5.9% of all deaths worldwide were attributed to alcohol intake (WHO, 2015). This statistic combined with the social, emotional, and other physical consequences of excessive alcohol use makes it is difficult to deny the ongoing need for preclinical research. Of greatest interest is identifying the treatments to promote and maintain abstinence in individuals diagnosed with an AUD. Remission, however, is often characterized by a chronic vulnerability to relapse, which is poorly understood. In fact, estimates of long-term relapse rates following remission are as high as 60%,

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depending on the treatment sought [1]. Lack of information on the neurobiological antece‐ dents and psychological determinates of relapse makes AUDs all the more problematic to address.

Further complicating our understanding of the persistent risk of relapse are the complex interactions between internal processes and the external environment. Most noted are the relationships that develop between environmental stimuli (cues), both contextual and discrete, and the internal states produced by alcohol. Over the course of alcohol use, specific cues become associated with the effects of alcohol through a Pavlovian learning process, whereby an associative (alcohol-cue) relationship is formed. Once the relationship has been acquired, these associative cues are able to autonomously produce psychological and physiological states that are powerful enough to elicit behavior responses. These responses have been suggested to play an important role in the development of AUDs and relapse.

Even after lengthy periods of abstinence, exposure to drug-associated cues can trigger intense feelings of craving and drive drug seeking [2–5], leading to relapse to drug use. When considering alcohol in particular, this lingering sensitivity to related cues is especially prob‐ lematic given the omnipresent nature of alcohol and alcohol-related cues in society. Therefore, it is important that the neurobiology of this phenomenon be understood so that more effective and durable treatments for alcoholism can be designed.

In the following sections, we describe common methodologies used to probe the neurobiology underlying primary and conditioned ethanol reward. Specifically, these methodological sections detail several commonly used animal models and tools to manipulate the brain. We then discuss the neural substrates that have been identified in ethanol-seeking behavior using these models and tools.
