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Morphine-Induced Apoptosis in the Ventral Tegmental Area and Hippocampus After the Development but not Extinction of Reward-Related Behaviors in Rats

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Abstract

Some data suggest that morphine induces apoptosis in neurons, while other evidences show that morphine could have protective effects against cell death. In this study, we suggested that there is a parallel role of morphine in reward circuitry and apoptosis processing. Therefore, we investigated the effect of morphine on modifications of apoptotic factors in the ventral tegmental area (VTA) and hippocampus (HPC) which are involved in the reward circuitry after the acquisition and extinction periods of conditioned place preference (CPP). In behavioral experiments, different doses of morphine (0.5, 5, and 10 mg/kg) and saline were examined in the CPP paradigm. Conditioning score and locomotor activity were recorded by Ethovision software after acquisition on the post-conditioning day, and days 4 and 8 of extinction periods. In order to investigate the molecular mechanisms in each group, we then dissected the brains and measured the expression of apoptotic factors in the VTA and HPC by western blotting analysis. All of the morphine-treated groups showed an increase of apoptotic factors in these regions during acquisition but not in extinction period. In the HPC, morphine significantly increased the ratio of Bax/Bcl-2, caspases-3, and PARP by the lowest dose (0.5 mg/kg), but, in the VTA, a considerable increase was seen in the dose of 5 mg/kg; promotion of apoptotic factors in the HPC and VTA insinuates that morphine can affect the molecular mechanisms that interfere with apoptosis through different receptors. Our findings suggest that a specific opioid receptor involves in modification of apoptotic factors expression in these areas. It seems that the reduction of cell death in response to high dose of morphine in the VTA and HPC may be due to activation of low affinity opioid receptors which are involved in neuroprotective features of morphine.

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Acknowledgments

The authors would like to thank Ms. Maryam Moslehi and Mr. Mahmoudreza Ramin for their comments and editing our manuscript. This study was supported by the grant (No. 90-821-A) from Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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There are no conflicts of interest.

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Authors and Affiliations

  1. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box 19615-1178, Tehran, Iran

    Yasaman Razavi, Shabnam Zeighamy Alamdary, Fariba Khodagholi & Abbas Haghparast

  2. Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

    Seyedeh-Najmeh Katebi

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  1. Yasaman Razavi
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  2. Shabnam Zeighamy Alamdary
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  3. Seyedeh-Najmeh Katebi
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Correspondence to Abbas Haghparast.

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Razavi, Y., Alamdary, S.Z., Katebi, SN. et al. Morphine-Induced Apoptosis in the Ventral Tegmental Area and Hippocampus After the Development but not Extinction of Reward-Related Behaviors in Rats. Cell Mol Neurobiol 34, 235–245 (2014). https://doi.org/10.1007/s10571-013-0007-8

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