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Oxytocin Intranasal Administration Affects Neural Networks Upstream of GNRH Neurons

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Abstract

The last decade has witnessed a surge in studies on the clinical applications of intranasal oxytocin as a method of enhancing social interaction. However, the molecular and cellular mechanisms underlying its function are not completely understood. Since oxytocin is involved in the regulation of hypothalamic-pituitary-gonadal axis by affecting the gonadotropin-releasing hormone (GNRH) system, the present study addressed whether intranasal application of oxytocin has a role in affecting GNRH expression in the male rat hypothalamus. In addition, we assessed expression of two excitatory (kisspeptin and neurokinin B) and two inhibitory (dynorphin and RFamide-related peptide-3) neuropeptides upstream of GNRH neurons as a possible route to relay oxytocin information. Here, adult male rats received 20, 40, or 80 μg oxytocin intranasally once a day for 10 consecutive days, and then, the posterior (PH) and anterior hypothalamus (AH) dissected for evaluation of target genes. Using qRT-PCR, we found that oxytocin treatment increased Gnrh mRNA levels in both the PH and AH. In addition, oxytocin at its highest dose increased kisspeptin expression in the AH by around 400%, whereas treatments, dose dependently decreased kisspeptin mRNA in the PH. The expression of neurokinin B was increased from the basal levels following the intervention. Furthermore, although intranasal-applied oxytocin decreased hypothalamic RFamide-related peptide-3 mRNA level, the dynorphin mRNA was not affected. These observations are consistent with the hypothesis that applications of intranasal oxytocin can affect the GNRH system.

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Acknowledgements

This study was financially supported by Shahid Beheshti University Grant No. 60092. The authors are thankful to the Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, for the technical support of this work.

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Correspondence to Homayoun Khazali.

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All experiments were conducted in the Laboratory Animal Center and in compliance with the recommendations of the Animal Care Committee of the Shahid Beheshti University, Tehran, Iran.

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The authors declare that they have no conflict of interest.

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Salehi, M.S., Khazali, H., Mahmoudi, F. et al. Oxytocin Intranasal Administration Affects Neural Networks Upstream of GNRH Neurons. J Mol Neurosci 62, 356–362 (2017). https://doi.org/10.1007/s12031-017-0943-8

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  • DOI: https://doi.org/10.1007/s12031-017-0943-8

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