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Dopamine D2 Receptor Antagonist Alters the Testosterone Release and Kisspeptin/GPR54 Signaling in Food-Restricted Rats

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Iranian Journal of Science and Technology, Transactions A: Science Aims and scope Submit manuscript

Abstract

It is well established that acute food restriction (FR) has a suppressive effect on the reproductive system that may be mediated through attenuating the kisspeptin/GPR54 signaling in the hypothalamus. Kisspeptin neurons have been shown to express the dopamine D2 receptor (D2R). The aim of the present study was to investigate the effect of chronic food restriction and/or antagonism of D2R by sulpiride on testosterone release and kisspeptin/GPR54 signaling in male rats. Sixty-six male Wistar rats, weighing-200 ± 20 g, were divided into seven groups including control, sham, 25%FR, 50%FR, 75%FR, sulpiride (50 µg/rat i.c.v., once at the end of treatment), 75%FR + sulpiride. FR was applied for 21 days. At the end, the mean serum testosterone level and the hypothalamic mRNAs expression of KiSS1, GPR54, D2R, and dopamine concentration were evaluated. The results demonstrated that the testosterone level significantly decreased in 50% and 75% food-restricted animals, and in sulpiride group, compared to control rats (P < 0.05). Injection of sulpiride to 75% food-restricted animals reduced the testosterone levels compared to all other groups (P < 0.05). Also, chronic 75%-FR significantly increased kisspeptin mRNA, dopamine concentration, but decreased D2R-mRNA (P < 0.05), and non-significantly decreased the GPR54mRNA (P > 0.05) compared to the control. Sulpiride injection to 75% food-restricted animals significantly decreased kisspeptin mRNA and increased dopamine concentration (P < 0.05), but had no significant effect on GPR54 or D2R-mRNAs expression, compared to 75% food-restricted group. In conclusion, we suggest that chronic food restriction decreases the testosterone release and then increases the kisspeptin/GPR54 signaling, and that the involvement of dopamine D2 receptor in these effects.

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Khatereh Noormohammadi and Farrin Babaei-Balderlou. The first draft of the manuscript was written by Farrin Babaei-Balderlou, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Farrin Babaei-Balderlou.

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The authors do not have any potential conflicts of interest to declare.

Human and Animal Rights

All experiments executed according to the Guide for the Care and Use of Laboratory Animals and approved by the institutional animal ethics committee.

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This manuscript does not contain any studies with human subjects performed by any of the authors.

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Nourmohammadi, K., Babaei-Balderlou, F. & Abtahi-Foroushani, S.M. Dopamine D2 Receptor Antagonist Alters the Testosterone Release and Kisspeptin/GPR54 Signaling in Food-Restricted Rats. Iran J Sci Technol Trans Sci 45, 1879–1886 (2021). https://doi.org/10.1007/s40995-021-01196-z

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  • DOI: https://doi.org/10.1007/s40995-021-01196-z

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