Novel use of a lipid-lowering fibrate medication to prevent nicotine reward and relapse: Preclinical findings

Leigh V. Panlilio, Zuzana Justinova, Paola Mascia, Marco Pistis, Antonio Luchicchi, Salvatore Lecca, Chanel Barnes, Godfrey H. Redhi, Jordan Adair, Stephen J. Heishman, Sevil Yasar, Mano Aliczki, Jozsef Haller, Steven R. Goldberg

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Experimental drugs that activate α-type peroxisome proliferator-activated receptors (PPARα) have recently been shown to reduce the rewarding effects of nicotine in animals, but these drugs have not been approved for human use. The fibrates are a class of PPARα-activating medications that are widely prescribed to improve lipid profiles and prevent cardiovascular disease, but these drugs have not been tested in animal models of nicotine reward. Here, we examine the effects of clofibrate, a representative of the fibrate class, on reward-related behavioral, electrophysiological, and neurochemical effects of nicotine in rats and squirrel monkeys. Clofibrate prevented the acquisition of nicotine-taking behavior in naive animals, substantially decreased nicotine taking in experienced animals, and counteracted the relapse-inducing effects of re-exposure to nicotine or nicotine-associated cues after a period of abstinence. In the central nervous system, clofibrate blocked nicotine's effects on neuronal firing in the ventral tegmental area and on dopamine release in the nucleus accumbens shell. All of these results suggest that fibrate medications might promote smoking cessation. The fact that fibrates are already approved for human use could expedite clinical trials and subsequent implementation of fibrates as a treatment for tobacco dependence, especially in smokers with abnormal lipid profiles.

Original languageEnglish
Pages (from-to)1838-1847
Number of pages10
JournalNeuropsychopharmacology
Volume37
Issue number8
DOIs
Publication statusPublished - Jul 1 2012

Keywords

  • PPARα
  • dopamine signaling
  • fibrate
  • nicotine
  • relapse
  • reward

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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    Panlilio, L. V., Justinova, Z., Mascia, P., Pistis, M., Luchicchi, A., Lecca, S., Barnes, C., Redhi, G. H., Adair, J., Heishman, S. J., Yasar, S., Aliczki, M., Haller, J., & Goldberg, S. R. (2012). Novel use of a lipid-lowering fibrate medication to prevent nicotine reward and relapse: Preclinical findings. Neuropsychopharmacology, 37(8), 1838-1847. https://doi.org/10.1038/npp.2012.31