Introduction to the Neuropsychopharmacology of Drug Addiction

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Drug addiction involves a three-stage cycle - binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation - that worsens over time and involves allostatic changes in the brain reward and stress systems. Two primary sources of reinforcement, positive and negative reinforcement, have been hypothesized to play a role in this allostatic process.

The construct of negative reinforcement is defined as drug taking that alleviates a negative emotional state. The negative emotional state that drives such negative reinforcement is hypothesized to derive from dysregulation of key neurochemical elements involved in the brain reward and stress systems. Acute withdrawal from all major drugs of abuse increases reward thresholds, decreases mesolimbic dopamine activity, increases anxiety-like responses, increases extracellular levels of corticotropin-releasing factor (CRF) in the central nucleus of the amygdala, and increases dynorphin in the ventral striatum. Excessive drug taking also activates CRF in the medial prefrontal cortex, paralleled by deficits in executive function that may facilitate the transition to compulsive-like responding.


drug addiction; negative reinforcement; reward system; stress system; allostatic process; reward threshold; dopamine; corticotropin-releasing factor; pharmacology; pharmacokinetics; neurobiology of addiction

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