Academic journal article Alcohol Research: Current Reviews

Common Biological Mechanisms of Alcohol Use Disorder and Post-Traumatic Stress Disorder

Academic journal article Alcohol Research: Current Reviews

Common Biological Mechanisms of Alcohol Use Disorder and Post-Traumatic Stress Disorder

Article excerpt

Alcohol use disorder (AUD) is one of the most common co-occurring disorders among individuals diagnosed with post-traumatic stress disorder (PTSD). (1) Many people who have PTSD use alcohol in an attempt to ameliorate debilitating symptoms such as anxiety and hyperarousal. Clinical and epidemiological studies have consistently reported that PTSD is associated with a threefold higher risk for developing AUD, and for individuals who have PTSD, the lifetime prevalence of AUD has been estimated at 40%. (2) The severity of PTSD symptoms is positively related to the level of alcohol use, and it also predicts alcohol craving in response to trauma- and alcohol-related cues. Despite the high rates of comorbidity, there is a substantial gap in understanding how traumatic experience leads to transition from initially controlled alcohol consumption (reward phase) to the development of alcohol-seeking and dependence (negative reinforcement phase). This review summarizes clinical observations and highlights findings from preclinical animal models, and focuses particularly on the alterations and dysfunctions in neural circuitry and stress hormone systems that may underlie enhanced vulnerability to AUD in context of PTSD (Figure 1).

Preclinical Models of PTSD and AUD

Animal model approaches

There are several procedures commonly used to create animal models of stress or PTSD and to employ stress components that are known to lead to enhanced risk for AUD. (3) Many procedures are simple, easy to implement, and effective at inducing a broad departure from endocrinological, physiological, and neurobiological homeostasis. (4) Also, both acute and chronic stressors can lead to physical and psychiatric pathology. First, we briefly describe a range of stress-related approaches to modeling the phenotypes of PTSD and AUD. Then, we review supporting studies in more detail, examining common biological components of both disorders.

Widely used physical stressors include exposure to immobilization, restraint, cold-water swimming, electric footshocks, and noxious stimuli. (4) Immobilization or restraint stress commonly is produced by confining a naive animal inside a bag or tube. Also, relevant naturalistic or ethological stressors have been used to trigger stress states. (4) Models of psychological stress include exposure to predator odor; an elevated platform; or a bright, open area; whereas models of social stress include social isolation, maternal deprivation, and social defeat. In some studies, more than one stressor is applied concomitantly to test the generality of a hypothesized mechanism or to enhance the intensity of desired responses.

Alcohol behaviors include various responses and changes elicited by alcohol exposure and withdrawal. Examples of these behaviors are alcohol craving, compulsive alcohol-seeking, excessive alcohol intake, alcohol dependence, and relapse. In this review, we survey the recent progress in animal modeling for two main aspects of AUD-related alcohol behaviors--alcohol consumption and alcohol-seeking. In general, experiments designed to investigate the effects of stress and alcohol behaviors can be divided into three categories. In the first category, alcohol-naive animals experience stress, then alcohol is introduced concurrently or after an incubation period. (5-7) In the second category, animals are familiarized to alcohol or to drinking alcohol before stress is introduced. (8) In the third category, animals develop alcohol behaviors, subsequently extinguish those behaviors, and then stress is introduced during a development, extinction, or reinstatement period. (9) In these experimental designs, alcohol behaviors are generally monitored through preference ratios and by measuring intake. Typically, animals have free access to water or an alcohol solution, and alcohol preference and intake are determined by the amount of liquid consumed and the number of approaches.

A considerable body of evidence suggests that stress triggers negative affective states and subsequent adaptive changes that lead to the development of AUD, so many animal models for AUD have focused on creating a condition in which a stress procedure precedes alcohol exposure (or re-exposure). …

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