Molecular Neurobiology

, Volume 56, Issue 2, pp 844–856 | Cite as

The Pharmacological Inhibition of Fatty Acid Amide Hydrolase Prevents Excitotoxic Damage in the Rat Striatum: Possible Involvement of CB1 Receptors Regulation

  • Gabriela Aguilera-Portillo
  • Edgar Rangel-López
  • Juana Villeda-Hernández
  • Anahí Chavarría
  • Pilar Castellanos
  • Zubeyir Elmazoglu
  • Çimen Karasu
  • Isaac Túnez
  • Gibrán Pedraza
  • Mina Königsberg
  • Abel SantamaríaEmail author


The endocannabinoid system (ECS) actively participates in several physiological processes within the central nervous system. Among such, its involvement in the downregulation of the N-methyl-D-aspartate receptor (NMDAr) through a modulatory input at the cannabinoid receptors (CBr) has been established. After its production via the kynurenine pathway (KP), quinolinic acid (QUIN) can act as an excitotoxin through the selective overactivation of NMDAr, thus participating in the onset and development of neurological disorders. In this work, we evaluated whether the pharmacological inhibition of fatty acid amide hydrolase (FAAH) by URB597, and the consequent increase in the endogenous levels of anandamide, can prevent the excitotoxic damage induced by QUIN. URB597 (0.3 mg/kg/day × 7 days, administered before, during and after the striatal lesion) exerted protective effects on the QUIN-induced motor (asymmetric behavior) and biochemical (lipid peroxidation and protein carbonylation) alterations in rats. URB597 also preserved the structural integrity of the striatum and prevented the neuronal loss (assessed as microtubule-associated protein-2 and glutamate decarboxylase localization) induced by QUIN (1 μL intrastriatal, 240 nmol/μL), while modified the early localization patterns of CBr1 (CB1) and NMDAr subunit 1 (NR1). Altogether, these findings support the concept that the pharmacological manipulation of the endocannabinoid system plays a neuroprotective role against excitotoxic insults in the central nervous system.


Endocannabinoid system Fatty acid amide hydrolase Cannabinoid receptor agonists Neuroprotection Excitotoxicity Oxidative stress 



Gabriela Aguilera-Portillo presents this article as the first author as it encompasses her work and efforts to obtain a Ph.D. degree at the Universidad Autónoma Metropolitana-Iztapalapa (Mexico). Authors express sincere gratitude to the Programa de Posgrado en Biología Experimental from the Universidad Autónoma Metropolitana-Iztapalapa for all the support provided throughout this study. We gratefully acknowledge the technical assistance of Dr. Ana Laura Colín-González. We also thank to the TUBITAK-SBAG (Project No.: 315S088).

Author Contributions

GAP, AC, CK, IT, MK, and AS conceived and designed the experiments. GAP, ERL, JVH, GP, and AS performed the experiments and analyzed the data. GAP and AS wrote the paper. ÇK, ZE, AC, MK, GAP, and AS developed the theory and contributed to the final version of the manuscript.


This work was supported by CONACyT-TUBITAK Grant 265991 (A.S.). Gabriela Aguilera-Portillo received a scholarship from CONACyT (CVU486539).

Compliance with Ethical Standards

Conflicts of Interest

The authors declare that they have no competing interests.

Research Involving Animals

Procedures carried out with animals were strictly developed to comply with the local guidelines for the use and care of laboratory animals (Norma Oficial Mexicana NOM-062-ZOO-2001), and the “Guidelines for the Use of Animals in Neuroscience Research” from the Society of Neuroscience. All experiments performed were timely approved by the Ethics Committee of the Instituto Nacional de Neurología y Neurocirugía. All efforts were made to minimize animal suffering during the experiments.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Gabriela Aguilera-Portillo
    • 1
    • 2
  • Edgar Rangel-López
    • 1
  • Juana Villeda-Hernández
    • 3
  • Anahí Chavarría
    • 4
  • Pilar Castellanos
    • 5
  • Zubeyir Elmazoglu
    • 6
  • Çimen Karasu
    • 6
  • Isaac Túnez
    • 7
  • Gibrán Pedraza
    • 8
  • Mina Königsberg
    • 8
  • Abel Santamaría
    • 1
    Email author
  1. 1.Laboratorio de Aminoácidos ExcitadoresInstituto Nacional de Neurología y Neurocirugía Manuel Velasco SuárezMexicoMexico
  2. 2.Posgrado en Biología Experimental, DCBSUniversidad Autónoma Metropolitana-IztapalapaMexicoMexico
  3. 3.Laboratorio de Patología ExperimentalInstituto Nacional de Neurología y NeurocirugíaMexicoMexico
  4. 4.Unidad de Investigación en Medicina Experimental, Facultad de MedicinaUniversidad Nacional Autónoma de MéxicoMexicoMexico
  5. 5.Departamento de Ingeniería Eléctrica, División de Ciencias Biológicas y de la SaludUniversidad Autónoma Metropolitana-IztapalapaMexicoMexico
  6. 6.Cellular Stress Response and Signal Transduction Research Laboratory, Faculty of Medicine, Department of Medical PharmacologyGazi UniversityAnkaraTurkey
  7. 7.Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC) & Departmento de Bioquímica y Biología Molecular, Facultad de Medicina y EnfermeríaUniversidad de CórdobaCordobaSpain
  8. 8.Departamento de Ciencias de la Salud, División de Ciencias Biológicas y de la SaludUniversidad Autónoma Metropolitana-IztapalapaMexicoMexico

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