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The Impact of Morphine on Reproductive Activity in Male Rats Is Regulated by Rf-Amid-Related Peptide-3 and Substance P Adjusting Hypothalamic Kisspeptin Expression

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Abstract

Obviously, opiates (e.g., morphine) are associated with the suppression and dysfunction of reproductive axis. It has been reported that substance P (SP) and RF-amid-related peptide-3 (RFRP-3) can exhibit anti-opioid effects in some regions of the nervous system. Moreover, SP and RFRP-3 are deemed as neuropeptides which exert modulatory and regulatory impacts on the function of the reproductive axis. The precise interactions of morphine with SP or RFRP-3 on the parameters of the reproductive activity, however, are not fully known. The present study was aimed to determine the impacts of the interaction of morphine either with SP or RFRP-3 on the hormonal and behavioral parameters of reproductive activity in male rats. In addition, it was aimed at determining whether the effects of these interactions rely on kisspeptin/G protein coupled receptor 54 (GPR54) pathway as the main upstream pulse generator and the mediator of the function of many inputs of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) system or not. Altogether, the resulted data from the sexual behavior tests, radioimmunoassay of LH/testosterone, and real-time quantitative PCR for the assessment of the expression of hypothalamic Kiss1, Gpr54, and Gnrh1 genes following concomitant administration of morphine with SP or RFRP-3 revealed that the suppressing effects of morphine on the parameters of reproductive axis activity can be affected by the administration of either RFRP-3 or SP. It is advocated that SP and RFRP-3, by the modulation of the expression of hypothalamic Kiss1, can possibly antagonize the effects of morphine on GnRH/LH system and sexual behavior.

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Funding

This study was financially and technically supported by Shahid Beheshti University, Tehran, Iran.

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Authors and Affiliations

  1. Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran

    Parastoo Rahdar, Homayoun Khazali, Abdolkarim Hosseini & Amin Raeisi

  2. Department of Foreign Languages, Faculty of Letters and Humanities, Shahid Beheshti University, Tehran, Iran

    Amin Raeisi

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  1. Parastoo Rahdar
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  2. Homayoun Khazali
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  3. Abdolkarim Hosseini
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  4. Amin Raeisi
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Correspondence to Homayoun Khazali.

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All experiments were carried out in the Laboratory of Animal Center and were in accordance with the recommendation of Animal Research Ethic Committee of Shahid Beheshti University, Tehran, Iran.

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Rahdar, P., Khazali, H., Hosseini, A. et al. The Impact of Morphine on Reproductive Activity in Male Rats Is Regulated by Rf-Amid-Related Peptide-3 and Substance P Adjusting Hypothalamic Kisspeptin Expression. J Mol Neurosci 69, 456–469 (2019). https://doi.org/10.1007/s12031-019-01375-z

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