Effects of cocaine in 5-lipoxygenase-deficient mice

M. Kurtuncu, N. Battista, T. Uz, A. D'Agostino, N. Dimitrijevic, N. Pasquariello, R. Manev, M. Maccarrone, H. Manev

Research output: Contribution to journalArticle

Abstract

5-Lipoxygenase (5-LOX), along with 12-lipoxygenase and cyclooxygenases, metabolizes arachidonic acid into eicosanoids. In rodents, 12-lipoxygenase deficiency alters behavioral responses to cocaine. We used 5-LOX-deficient mice and their controls to investigate cocaine's actions. After repeated cocaine injections, the increase in locomotor activity was greater in 5-LOX-deficient mice. Since the 5-LOX pathway may regulate the levels/metabolism of arachidonoylethanolamide (AEA) we assayed the AEA levels in the striatum, the binding of the endogenous AEA to the cannabinoid receptor CB1R, and anandamide hydrolase (FAAH) activity in the striatum, hippocampus, and cortex. Striatal AEA levels decreased after repeated cocaine injections. Cocaine also decreased CB1R binding in all brain regions studied and the only significant differences between 5-LOX-deficient and control mice was the greater hippocampal FAAH activity in 5-LOX-deficient mice. Our results demonstrated that a 5-LOX deficiency alters sensitivity to repeated cocaine. It should be investigated whether a human 5-LOX gene polymorphism affects cocaine's actions.

Original languageEnglish
Pages (from-to)389-395
Number of pages7
JournalJournal of Neural Transmission
Volume115
Issue number3
DOIs
Publication statusPublished - Mar 2008

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Keywords

  • 5-Lipoxygenase
  • Anandamide
  • Anandamide hydrolase (FAAH)
  • Cocaine

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kurtuncu, M., Battista, N., Uz, T., D'Agostino, A., Dimitrijevic, N., Pasquariello, N., Manev, R., Maccarrone, M., & Manev, H. (2008). Effects of cocaine in 5-lipoxygenase-deficient mice. Journal of Neural Transmission, 115(3), 389-395. https://doi.org/10.1007/s00702-007-0848-8