Pathophysiological basis of vulnerability to drug abuse: role of an interaction between stress, glucocorticoids, and dopaminergic neurons

Annu Rev Pharmacol Toxicol. 1996:36:359-78. doi: 10.1146/


Research on drug abuse has recently focused on understanding the vulnerability to develop addiction that is present in certain individuals. These investigations suggest that addiction results from an interaction between drugs and specific individual substrates. Differences in the propensity to develop drug intake can be demonstrated in animals with equal access to drugs under stable laboratory conditions and can be predicted by drug-independent behaviors. Stress, corticosterone, and mesencephalic dopaminergic neurons seem to be organized in a pathophysiological chain determining such a vulnerability. An increased corticosterone secretion, or a higher sensitivity to the effects of this hormone, either naturally present in certain individuals or induced by stress in others, increases the vulnerability to develop drug intake, via an enhancement of the activity of mesencephalic dopaminergic neurons. These findings suggest that addiction therapies should counteract the biological peculiarity that leads some individuals to respond in a pathophysiological way to drugs.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dopamine / metabolism*
  • Drug Interactions
  • Drug Tolerance
  • Glucocorticoids / metabolism*
  • Humans
  • Neurons / drug effects*
  • Neurons / physiology
  • Stress, Physiological / complications
  • Stress, Physiological / physiopathology*
  • Substance-Related Disorders / etiology
  • Substance-Related Disorders / physiopathology*
  • Substance-Related Disorders / therapy


  • Glucocorticoids
  • Dopamine