Abstract and Keywords
Drug addiction can be conceptualized as a disorder that progresses from neurobiological mechanisms involved in positive reinforcement to mechanisms involved in negative reinforcement. Neurobiological substrates for the positive reinforcement of drug abuse involve activation of the brain’s incentive salience and reward systems, such as dopamine and opioid peptides, and neurobiological substrates for the negative reinforcement of drug addiction involve the brain stress systems, such as corticotropin-releasing factor (CRF), norepinephrine, and dynorphin in the ventral striatum and extended amygdala. Decreased function of brain antistress systems further contributes to motivational dysfunction. A brain stress response system is hypothesized to be dysregulated by acute excessive drug intake, sensitized during repeated withdrawal, persist into protracted abstinence, and contribute to the allostatic changes in motivation associated with addiction. From a theoretical perspective, the combination of loss of reward function and recruitment of brain stress systems drives the compulsivity of addiction and provides a rich neurobiological substrate for therapeutic interventions.
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