Peroxisome Proliferator-Activated Nuclear Receptors and Drug Addiction

  • Paola Mascia
  • Gianluigi Tanda
  • Sevil Yasar
  • Stephen J. Heishman
  • Steven R. Goldberg
Part of the The Receptors book series (REC, volume 24)


Recent research with animal models of human drug dependence has demonstrated that a receptor related to the endogenous cannabinoid system, the peroxisome proliferator-activated alpha nuclear receptor (PPARα), which regulates genes involved in lipid metabolism and inflammatory responses, is a viable target for treating nicotine dependence. The endogenous ligands for PPARα, oleoylethanolamide and palmitoylethanolamide, are structurally similar to anandamide, an endogenous ligand for cannabinoid receptors, and all three share the same degrading mechanism. Anandamide also has been reported to act at PPARα, as well as PPARγ, suggesting overlap and potential interactions between endogenous cannabinoid and PPAR receptor systems. In rat and nonhuman primate models of human tobacco dependence, PPARα agonists counteract neurochemical effects of nicotine in the brain that mediate nicotine’s rewarding effects and suppress nicotine self-administration behavior and relapse to nicotine-seeking behavior, suggesting PPARα agonists as a treatment for tobacco dependence. In other studies, the PPARγ agonists, pioglitazone and rosiglitazone, that belong to the class of thiazolidinediones (TZDs), which are used for the treatment of insulin resistance and type 2 diabetes, suppress alcohol-drinking behavior and relapse to alcohol-seeking behavior, as well as signs of alcohol withdrawal in rats, suggesting TZDs as a treatment for alcohol dependence. In addition, both PPARα and PPARγ activation suppress sensitization that develops the effects of psychostimulants and opioids when they are administered chronically. Since behavioral sensitization is believed to contribute to the development of drug dependence, these findings suggest a general utility of PPAR agonists as treatments for drug dependence.


Ventral Tegmental Area Conditioned Place Preference Behavioral Sensitization Fatty Acid Amide Hydrolase Fatty Acid Amide Hydrolase Inhibition 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This research and preparation of the chapter was supported in part by the Intramural Research Program of the NIH, National Institute on Drug Abuse and by the Division of Geriatric Medicine and Gerontology of Johns Hopkins University School of Medicine.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Paola Mascia
    • 1
  • Gianluigi Tanda
    • 2
  • Sevil Yasar
    • 3
  • Stephen J. Heishman
    • 4
  • Steven R. Goldberg
    • 1
  1. 1.Department of Health and Human ServicesPreclinical Pharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of HealthBaltimoreUSA
  2. 2.Department of Health and Human ServicesPsychobiology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of HealthBaltimoreUSA
  3. 3.Division of Geriatric Medicine and GerontologyJohns Hopkins University School of MedicineBaltimoreUSA
  4. 4.Department of Health and Human ServicesNicotine Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of HealthBaltimoreUSA

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