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Neurobiological mechanisms for opponent motivational processes in addiction

Academic Article
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Overview

authors

  • Koob, George
  • Le Moal, Michel

publication date

  • October 2008

journal

  • Philosophical Transactions of the Royal Society B-Biological Sciences  Journal

abstract

  • The conceptualization of drug addiction as a compulsive disorder with excessive drug intake and loss of control over intake requires motivational mechanisms. Opponent process as a motivational theory for the negative reinforcement of drug dependence has long required a neurobiological explanation. Key neurochemical elements involved in reward and stress within basal forebrain structures involving the ventral striatum and extended amygdala are hypothesized to be dysregulated in addiction to convey the opponent motivational processes that drive dependence. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission such as dopamine and opioid peptides in the ventral striatum, but also recruitment of brain stress systems such as corticotropin-releasing factor (CRF), noradrenaline and dynorphin in the extended amygdala. Acute withdrawal from all major drugs of abuse produces increases in reward thresholds, anxiety-like responses and extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence and to contribute to stress-induced relapse. The combination of loss of reward function and recruitment of brain stress systems provides a powerful neurochemical basis for the long hypothesized opponent motivational processes responsible for the negative reinforcement driving addiction.

subject areas

  • Amygdala
  • Basal Ganglia
  • Corticotropin-Releasing Hormone
  • Dynorphins
  • Humans
  • Motivation
  • Neurobiology
  • Norepinephrine
  • Recurrence
  • Stress, Physiological
  • Substance Withdrawal Syndrome
  • Substance-Related Disorders
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Research

keywords

  • addiction
  • corticotropin-releasing factor
  • extended amygdala
  • opponent process
  • stress
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Identity

PubMed Central ID

  • PMC2607326

International Standard Serial Number (ISSN)

  • 0962-8436

Digital Object Identifier (DOI)

  • 10.1098/rstb.2008.0094

PubMed ID

  • 18653439
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Additional Document Info

start page

  • 3113

end page

  • 3123

volume

  • 363

issue

  • 1507

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