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Stress, dysregulation of drug reward pathways, and the transition to drug dependence

Academic Article
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Overview

authors

  • Koob, George
  • Kreek, M. J.

publication date

  • August 2007

journal

  • American Journal of Psychiatry  Journal

abstract

  • This review provides a neuroadaptive perspective regarding the role of the hormonal and brain stress systems in drug addiction with a focus on the changes that occur during the transition from limited access to drugs to long-term compulsive use of drugs. A dramatic escalation in drug intake with extended access to drug self-administration is characterized by a dysregulation of brain reward pathways. Hormonal studies using an experimenter-administered cocaine binge model and an escalation self-administration model have revealed large increases in ACTH and corticosterone in rats during an acute binge with attenuation during the chronic binge stage and a reactivation of the hypothalamic-pituitary-adrenal axis during acute withdrawal. The activation of the hypothalamic-pituitary-adrenal axis with cocaine appears to depend on feed-forward activation of the mesolimbic dopamine system. At the same time, escalation in drug intake with either extended access or dependence-induction produces an activation of the brain stress system's corticotropin-releasing factor outside of the hypothalamus in the extended amygdala, which is particularly evident during acute withdrawal. A model of the role of different levels of hormonal/brain stress activation in addiction is presented that has heuristic value for understanding individual vulnerability to drug dependence and novel treatments for the disorder.

subject areas

  • Animals
  • Behavior, Addictive
  • Brain
  • Corticotropin-Releasing Hormone
  • Disease Models, Animal
  • Electrodes, Implanted
  • Hydrocortisone
  • Hypothalamus
  • Illicit Drugs
  • Models, Neurological
  • Prolactin
  • Rats
  • Reinforcement (Psychology)
  • Reward
  • Self Administration
  • Stress, Physiological
  • Substance-Related Disorders
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Identity

PubMed Central ID

  • PMC2837343

International Standard Serial Number (ISSN)

  • 0002-953X

Digital Object Identifier (DOI)

  • 10.1176/appi.ajp.2007.05030503

PubMed ID

  • 17671276
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Additional Document Info

start page

  • 1149

end page

  • 1159

volume

  • 164

issue

  • 8

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