New concepts in cocaine addiction: the dopamine depletion hypothesis

Neurosci Biobehav Rev. 1985 Fall;9(3):469-77. doi: 10.1016/0149-7634(85)90022-3.


Euphoric properties of cocaine lead to the development of chronic abuse, and appear to involve the acute activation of central DA neuronal systems. This is based upon known effects of cocaine on DA neurons, and the role played by DA in reward states and self-stimulation behavior. With chronic cocaine use, neurotransmitter and neuroendocrine alterations occur. DA depletion is hypothesized to result from overstimulation of these neurons and excessive synaptic metabolism of the neurotransmitter. DA depletion may underlie dysphoric aspects of cocaine abstinence, and cocaine urges. Neurochemical disruptions caused by cocaine are consistent with the concept of "physical" rather than "psychological" addiction. Possible pharmacological interventions in cocaine addiction are outlined and the psychological approach to these patients is discussed.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / drug effects*
  • Cocaine* / pharmacology
  • Conditioning, Operant
  • Dopamine / metabolism
  • Euphoria / drug effects
  • Female
  • Humans
  • Hydrocortisone / metabolism
  • Hypothalamo-Hypophyseal System / drug effects
  • Male
  • Mice
  • Models, Neurological
  • Models, Psychological
  • Prolactin / metabolism
  • Rats
  • Reward
  • Serotonin / metabolism
  • Substance Withdrawal Syndrome
  • Substance-Related Disorders* / etiology
  • Substance-Related Disorders* / therapy
  • Synaptic Transmission / drug effects
  • Thyroid Gland / drug effects
  • Thyrotropin-Releasing Hormone / metabolism


  • Serotonin
  • Thyrotropin-Releasing Hormone
  • Prolactin
  • Cocaine
  • Dopamine
  • Hydrocortisone