Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 392, Issue 11, pp 1383–1391 | Cite as

Effect of oleuropein on morphine-induced hippocampus neurotoxicity and memory impairments in rats

  • Farhad Shibani
  • Ali Sahamsizadeh
  • Iman Fatemi
  • Mohammad Allahtavakoli
  • Jalal Hasanshahi
  • Mohammadreza Rahmani
  • Mahdieh Azin
  • Mahsa Hassanipour
  • Nazanin Mozafari
  • Ayat KaeidiEmail author
Original Article


Oleuropein, as an olive leaf extract antioxidant polyphenol, has been reported to be a free radical scavenger. This study was done to investigate the effects of oleuropein, against morphine-induced hippocampus neurotoxicity and memory impairment in rats. The Morris water maze (MWM) test was used to assess the effect of oleuropein (5, 15, and 30 mg/kg, i.p., co-administrated with morphine) on spatial learning and memory of male Wistar rats which were treated with morphine sulfate (45 mg/kg, s.c., 4 weeks). In order to evaluate the cleaved caspase-3, Bax, and Bcl2 protein expression (as biochemical markers of apoptosis) in CA1 area of hippocampus tissue, the western blot test was used. Also, to evaluate the oxidative stress status of hippocampus CA1 area tissue, the malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, and glutathione peroxidase (GPx) activity were assessed. The data showed that oleuropein treatment (15 and 30 mg/kg) improves the spatial learning and memory impairments in morphine-treated animals. Also, oleuropein treatment decreased the apoptosis and oxidative stress levels in the hippocampus CA1 area of morphine-treated rats. Oleuropein can prevent the spatial learning and memory impairments in morphine-treated rats. Molecular mechanisms underlying the observed effects could be at least partially related to the inhibition of neuronal apoptosis and oxidative stress in the hippocampus CA1 area of morphine-treated rats.


Oleuropein Morphine Learning and memory Hippocampus Apoptosis Oxidative stress 


Author contributions

Conceived and designed the experiments: AK and ASH. Performed the experiments: FSH, NM, MR, and IF. Analyzed the data: AK and MAT. Contributed reagents/materials/analysis tools: MH, MA, and JH. Wrote the paper: AK and FSH.

Funding information

This study received funding from Rafsanjan University of Medical Sciences (grant numbers 20/1058).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Farhad Shibani
    • 1
    • 2
  • Ali Sahamsizadeh
    • 2
  • Iman Fatemi
    • 3
  • Mohammad Allahtavakoli
    • 2
  • Jalal Hasanshahi
    • 2
  • Mohammadreza Rahmani
    • 1
  • Mahdieh Azin
    • 2
  • Mahsa Hassanipour
    • 2
  • Nazanin Mozafari
    • 1
  • Ayat Kaeidi
    • 2
    Email author
  1. 1.Physiology-Pharmacology Research Center, Research Institute of Basic Medical SciencesRafsanjan University of Medical SciencesRafsanjanIran
  2. 2.Department of Physiology and PharmacologyRafsanjan University of Medical SciencesRafsanjanIran
  3. 3.Research Center of Tropical and Infectious DiseasesKerman University of Medical SciencesKermanIran

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