Venue: Centre Broca
George F. Koob, Ph. D.
Director, National Institute on Alcohol Abuse and Alcoholism
Senior Investigator, National Institute on Drug Abuse
Bethesda, MD
Invited by Serge Ahmed (INCIA)
Title
Neurobiology of Alcohol and Opioid Addiction: A hyperkatifeia, negative reinforcement, and allostasis perspective
Abstract
Addiction is a chronically relapsing disorder 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 is defined as drug taking that alleviates a negative emotional state or hyperkatifeia (pain, hypohedonia, dysphoria, anxiety, hyperalgesia, irritability, and sleep disturbances) that is created by drug abstinence following excessive drug consumption. In humans, and animal models, repeated misuse of drugs results in hyperkatifeia as reflected in increased reward thresholds, decreased pain thresholds, anxiety-like and dysphoric-like responses. Such hyperkatifeia that drives negative reinforcement is hypothesized to derive from dysregulation of key neurochemical circuits within the brain reward and stress systems. Thus, 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 withdrawal, and contributes to the development and persistence of compulsive alcohol seeking. The construct of negative reinforcement fits a framework of allostasis where other allostatic loads such as genetics/ epigenetics, childhood trauma, and social determinants of health join hyperkatifeia in driving addiction.