Addiction is defined as a chronic relapsing disorder, in which individuals often return to compulsive drug taking after a period of abstinence (Koob and Volkow, 2010, Koob and Volkow, 2016). In an addicted individual, intense preoccupation with obtaining the abused substance develops and often precedes the somatic signs of withdrawal. This behavior, commonly described as craving, represents a shift from goal-directed behavior to habit driven (compulsive) behavior that results from drug-conditioned reinforcement, altered incentive motivation and maladaptive stimulus-response learning (Koob and Volkow, 2010). In other words, continued heavy use becomes a conditioned response to relieve and avoid withdrawal symptoms (e.g., withdrawal-induced seizures in alcoholics (Tabakoff and Hoffman, 2013).This stage of addiction primarily involves loss of prefrontal cortical executive control over intake (Everitt and Robbins, 2013). Hypofunction of cortical circuits are thought to play a permissive role in which subcortical structures that drive addiction are no longer inhibited (Koob, 2013c). As a result, circuits of the extended amygdala that mediate enhanced reactivity to stressful stimuli, dysphoria, anhedonia and increased craving drive behavior, ultimately leading to drug consumption (relapse).
