Addiction and dose response: the psychomotor stimulant theory of addiction reveals that hormetic dose responses are dominant

Crit Rev Toxicol. 2008;38(7):599-617. doi: 10.1080/10408440802026315.


In 1987 Wise and Bozarth proposed a psychomotor stimulant theory of addiction whose most consistent feature was enhanced forward (horizontal) locomotion. While controversial, the theory of Wise and Bozarth has had substantial impact on addiction behavior theory over the past two decades, being cited over 1,400 times. The present assessment places the theoretical formulation of Wise and Bozarth (1987) within a dose-response framework. This analysis demonstrates that the psychomotor stimulant effects of addictive drugs routinely display biphasic dose-response relationships that are consistent with the quantitative features of the hormetic dose-response model. This is the case, regardless of addictive agent, animal model, and experimental protocol employed. Not only do these findings suggest an important role for the hormetic dose response model in the assessment of addictive behaviors, they also further extend the generalizability of the hormesis dose-response model concept within the biomedical sciences.

Publication types

  • Review

MeSH terms

  • Adaptation, Physiological*
  • Animals
  • Central Nervous System Stimulants / adverse effects*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug*
  • Humans
  • Psychomotor Agitation / etiology*
  • Psychomotor Agitation / physiopathology
  • Psychomotor Performance / drug effects*
  • Substance-Related Disorders / etiology*
  • Substance-Related Disorders / physiopathology


  • Central Nervous System Stimulants