Impact of different intensities of forced exercise on deficits of spatial and aversive memory, anxiety-like behavior, and hippocampal BDNF during morphine abstinence period in male rats

  • Azadeh Shahroodi
  • Fatemeh Mohammadi
  • Abbas Ali Vafaei
  • Hossein Miladi-Gorji
  • Ahmad Reza Bandegi
  • Ali Rashidy-PourEmail author
Original Article


Forced exercise can alleviate cognitive-behavioral deficits in an experimental model of addiction. However, the effects of different intensities of forced exercise in improving behavioral, cognitive and biochemical deficits during morphine abstinence period are not well investigated. Thus, the current work examined the effects of different loads of forced exercise on cognition functions, anxiety behavior and BDNF changes in the hippocampus, and prefrontal cortex (PFC), and also serum levels of BDNF and corticosterone during the abstinent period in male rats. Animals received morphine injections (10 mg/kg, twice a day) for 10 consecutive days. Then, the animals were exposed to a 4-week forced exercise training program under low, moderate or high intensities (30 min per session on 5 days a week), which accompanied by behavioral and biochemical tests. In Experiment 1, anxiety-like behaviors using elevated plus maze (EPM), and light/dark box (L/D box) were examined. In Experiment 2, cognitive functions using T-maze alteration and passive avoidance tasks were tested, which accompanied by BDNF measurements in the hippocampus and PFC. In Experiment 3, serum levels of BDNF and corticosterone following the termination of forced exercise regimen were measured. Morphine-abstinent animals exhibited anxiogenic -like behaviors in the EPM, but not L/D box. They also exhibited impaired T-maze alternation performance and passive avoidance memory, and a decline in hippocampal BDNF, but not PFC. Forced exercise at a moderate intensity alleviated anxiety, cognitive and BDNF defects in morphine-abstinent animals. The high load exercise enhanced serum levels of corticosterone in both saline and morphine groups. Thus, regular moderate forced exercise may be beneficial in preserving cognitive and mood functions in male addicts during the abstinent period and drug rehabilitation.


Forced exercise Exercise intensity Morphine abstinence Memory Anxiety Brain-derived neurotrophic factor 



Prefrontal cortex


Elevated plus maze

L/D box

Light and Dark box


Brain derived neurotropic factor


Open arm entry


Open arm time



The authors wish to thank the Research Center of Physiology of Semnan University of Medical Sciences for providing all facilities for this research.

Authors’ contributions

A.S, A.A.V and A.R.P. designed the overall study and wrote the paper. A.S, F.M. A.R.B and H.M-G conducted the research, collected data and carried out the lab work. A.S, and A.R.P carried out the statistical analysis and mostly drafted the manuscript. A.R.P. coordinated and supervised the study. All authors approved the manuscript.

Funding information

This work was supported by grants from Cognitive Sciences and Technologies Council of Iran and Semnan University of Medical Sciences (Semnan, Iran).

Compliance with ethical standards

Ethical approval

The Ethical Review Board of SUMS approved the experimental protocol. All experimental trials were conducted in agreement with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. All behavioral tests were performed between 8:00 am and 1:00 pm. Different experimenters who were blinded to the experimental groups performed behavioral and biochemical tests.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Azadeh Shahroodi
    • 1
    • 2
  • Fatemeh Mohammadi
    • 1
    • 2
  • Abbas Ali Vafaei
    • 2
    • 3
  • Hossein Miladi-Gorji
    • 2
    • 3
  • Ahmad Reza Bandegi
    • 2
    • 4
  • Ali Rashidy-Pour
    • 2
    • 3
    Email author
  1. 1.Student Research Committee, School of MedicineSemnan University of Medical SciencesSemnanIran
  2. 2.Research Center of PhysiologySemnan University of Medical SciencesSemnanIran
  3. 3.Department of Physiology, School of MedicineSemnan University of Medical SciencesSemnanIran
  4. 4.Laboratory of Endocrine Research, School of MedicineSemnan University of Medical SciencesSemnanIran

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