Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Pharmacol Ther. 2007 Nov;116(2):306-21. Epub 2007 Jul 24.

Dynorphin and the pathophysiology of drug addiction.

Author information

  • 1Integrative Neuroscience Section, NIH/NIDA Intramural Research Program, 333 Cassell Drive, Baltimore, MD 21224, USA. tshippen@intra.nida.nih.gov

Abstract

Drug addiction is a chronic relapsing disease in which drug administration becomes the primary stimulus that drives behavior regardless of the adverse consequence that may ensue. As drug use becomes more compulsive, motivation for natural rewards that normally drive behavior decreases. The discontinuation of drug use is associated with somatic signs of withdrawal, dysphoria, anxiety, and anhedonia. These consequences of drug use are thought to contribute to the maintenance of drug use and to the reinstatement of compulsive drug use that occurs during the early phase of abstinence. Even, however, after prolonged periods of abstinence, 80-90% of human addicts relapse to addiction, suggesting that repeated drug use produces enduring changes in brain circuits that subserve incentive motivation and stimulus-response (habit) learning. A major goal of addiction research is the identification of the neural mechanisms by which drugs of abuse produce these effects. This article will review data showing that the dynorphin/kappa-opioid receptor (KOPr) system serves an essential function in opposing alterations in behavior and brain neurochemistry that occur as a consequence of repeated drug use and that aberrant activity of this system may not only contribute to the dysregulation of behavior that characterizes addiction but to individual differences in vulnerability to the pharmacological actions of cocaine and alcohol. We will provide evidence that the repeated administration of cocaine and alcohol up-regulates the dynorphin/KOPr system and that pharmacological treatments that target this system may prove effective in the treatment of drug addiction.

PMID:
17868902
[PubMed - indexed for MEDLINE]
PMCID:
PMC2939016
Free PMC Article

Images from this publication.See all images (1)Free text

Fig.1
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk