Alcohol Dependence Conceptualized as a Stress Disorder

Alcohol use disorder is a chronically relapsing disorder that involves (1) compulsivity to seek and take alcohol, (2) difficulty in limiting alcohol intake, and (3) emergence of a negative emotional state (e.g., dysphoria, anxiety, irritability) in the absence of alcohol. Alcohol addiction encompasses a three-stage cycle that becomes more intense as alcohol use progresses: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. These stages engage neuroadaptations in brain circuits that involve the basal ganglia (reward hypofunction), extended amygdala (stress sensitization), and prefrontal cortex (executive function disorder). This chapter discusses key neuroadaptations in the hypothalamic and extrahypothalamic stress systems and the critical role of glucocorticoid receptors. These neuroadaptations contribute to negative emotional states that powerfully drive compulsive alcohol drinking and seeking. These changes in association with a disruption of prefrontal cortex function that lead to cognitive deficits and poor decision making contribute to the chronic relapsing nature of alcohol dependence.