The Journal of Physiological Sciences

, Volume 69, Issue 2, pp 409–419 | Cite as

Different doses of methamphetamine alter long-term potentiation, level of BDNF and neuronal apoptosis in the hippocampus of reinstated rats

  • Siamak Shahidi
  • Alireza Komaki
  • Reihaneh SadeghianEmail author
  • Sara Soleimani Asl
Original Paper


Methamphetamine (METH) is a psychostimulant. The precise mechanisms of its effects remain unknown and current relapse treatments have low efficacy. However, brain-derived neurotrophic factor (BDNF) and neuronal plasticity are essential contributors, despite paradoxical reports and a lack of comprehensive studies. Therefore, we investigated the effects of different doses of METH on long-term potentiation (LTP), BDNF expression and neuronal apoptosis in the hippocampus of reinstated rats. Rats were injected intraperitoneally with METH (1, 5, or 10 mg/kg) or saline, and trained in a conditioned place preference paradigm. Following implementation of the reinstatement model, electrophysiology, western blotting and TUNEL assay were performed to assess behavior, LTP components, BDNF expression, and neuronal apoptosis, respectively. The results demonstrated that the preference scores, population spike amplitude and BDNF expression markedly decreased in the METH (10 mg/kg) group compared with the other groups. In contrast, METH (5 mg/kg) significantly increased these factors more than the control group. There was no change in variables between METH (1 mg/kg) and the control group. Also, apoptosis of the hippocampus was increased in the METH (10 mg/kg) group compared with the METH (5 mg/kg) group. These results suggest that alterations in synaptic plasticity, expression of BDNF and neuronal apoptosis in the hippocampus has a vital role in the context-induced reinstatement of METH seeking.


Reinstatement Conditioned place preference Long-term potentiation Brain derived neurotrophic factor Neuronal apoptosis Methamphetamine 



We thank Drug Control Headquarters of the Police, Hamadan, Iran, the vice-chancellor for Research and Technology, Hamadan University of Medical Sciences (no. 9407073722), and the Cognitive Science and Technologies Council (no. 3078), Tehran, who supported this study in the provision of equipment and supplies.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest for any of them.

Ethical approval

All animal experimental procedures were performed in accordance with the guidelines for proper conduct of animal experiments issued by the Ethics Committee of the Hamadan University of Medical Sciences (IR.Umsha.REC.1394.200), and performed according to The Guide for Care and Use of Laboratory Animals published by the National Institutes of Health, United States (NIH Publication No. 85-23, revised 1985).


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Copyright information

© The Physiological Society of Japan and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Neurophysiology Research CenterHamadan University of Medical SciencesHamadanIran
  2. 2.Medical Toxicology and Drug Abuse Research CenterBirjand University of Medical SciencesBirjandIran
  3. 3.Anatomy Departments, School of MedicineHamadan University of Medical SciencesHamadanIran

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