Alcohol and Drug addiction are chronically relapsing disorders characterized by compulsive drug seeking that is hypothesized to derive from multiple sources of motivational dysregulation, one of which is negative reinforcement driven by the emotional pain of alcohol withdrawal and protracted abstinence. The construct of negative reinforcement, defined as alcohol taking that alleviates a negative emotional state or hyperkatifeia (pain, hypohedonia, dysphoria, anxiety, hyperalgesia, irritability, and sleep disturbances) that is created by alcohol abstinence. In animal models, repeated misuse of alcohol results in negative emotion-like states reflected in increased reward thresholds, decreased pain thresholds, anxiety-like and dysphoric-like responses. Such negative emotional-like states that drive negative reinforcement are hypothesized to derive from dysregulation of key neurochemical circuits within the brain reward and stress systems (corticotropin-releasing factor, dynorphin, norepinephrine, hypocretin, vasopressin, glucocorticoids, and neuroimmune factors) in the extended amygdala. Compelling evidence exists to argue that hyperkatifeia triggered by acute excessive drug intake, is sensitized during the development of compulsive alcohol taking with repeated withdrawal, persists into protracted abstinence, and contributes to the development and persistence of compulsive alcohol seeking. Significant overlap in the engagement in the addiction of circuits mediating brain emotional pain, and brain physical pain may help explain the prominent role of alcohol drugs in “deaths of despair”.
After attending this presentation, participants will be able to:
1) Discuss the theoretical framework of hyperkatifeia and negative reinforcement that drives drug seeking in the withdrawal/negative affect stage; and,
2) Outline the changes in the brain neurocircuitry that mediate hyperkatifeia and negative reinforcement in the withdrawal/negative affect stage.
