Mu Opioid Agonistic Effect on Neuropeptide Gene Expression Levels Involved in Hypothalamic Feeding Regulation

Year 2025, Volume: 6 Issue: 1, 1 - 7, 31.01.2025

Fatma Bedia Karakaya Cimen , Zeliha Erkaya Turan , Aysu Sen , Kaniye Zeynep Caliskan Sak , Canan Eroglu Günes , Ercan Kurar , Yasin Ali Cimen , Selim Kutlu

https://doi.org/10.47482/acmr.1608775

Abstract

Background: The regulation of food intake in the hypothalamus is one of most complicated through the integration of various neuroendocrine mechanisms. In this region, orexigenic and anorexigenic peptides play a role by responding to different stimuli. Additionally, central opioidergic systems are involved in the regulation of feeding behavior. Several neuropeptides expressed in the hypothalamus also contribute to the regulation of food intake. The aim of this study was to investigate the effects of mu opioidergic agonist/antagonist molecules on both orexigenic and anorexigenic peptides gene expression levels in the hypothalamus.
Methods: In our study, 48 male Wistar Albino rats were divided into 4 groups as control, morphine, naloxone and morphine+naloxone. The control group received subcutaneous SF solution for 5 days; morphine group received morphine at a dose of 10 mg/kg/day for 5 days; naloxone group SF was administered for 5 days and naloxone at a dose of 3 mg/kg 1.5 hours after the last injection: morphine+naloxone group received naloxone 1.5 hours after 5 days of morphine injection. Hypothalamus tissues were isolated from brains at the end of experimental period. Anorexigenic and orexigenic peptide expression levels were analysed by RT-PCR method. Differences between groups were statistically analyzed using one-way factorial ANOVA and Tukey post-hoc test.
Results: Morphine administration results in a decrease in the expression levels of OX2R and LepR genes, but did not change ORXA, OX1R, AgRP, NPY, POMC gene expression. Naloxone administration increased AgRP and NPY expression while decreasing OX2R, LepR and APLNR gene expression levels.
Conclusions: Our findings suggest that morphine may affect the gene expression of molecules related to regulation of nutrition and metabolism in the hypothalamus. Further studies are needed to clarify the possible mechanistic effects of mu opiodergic activity on the central control of feeding in morphine dependence manner.

Keywords

AgRP, apelin, hypothalamus, neuropeptides, NPY, morphine dependence, POMC, rat

Ethical Statement

This project has been approved by Necmettin Erbakan University Experimental Animals Local Ethics Committee (Project Number: 2023-041)

Supporting Institution

This study was supported by Necmettin Erbakan University Scientific Research Projects Coordination Office with project number 23YL18003.

Project Number

23YL18003

Thanks

We would like to thank Necmettin Erbakan University Scientific Research Projects Coordination Office for their support.

Hipotalamik Beslenmenin Düzenlenmesinde Rol Oynayan Nöropeptid Gen Ekspresyon Düzeyleri Üzerinde Mu Opioid Agonistik Etkisi

Abstract

Arkaplan: Gıda alımının düzenlenmesi hipotalamusta çeşitli nöroendokrin mekanizmaların entegrasyonu yoluyla gerçekleşir. Bu bölgede oreksijenik ve anoreksijenik peptidler farklı uyaranlara yanıt vererek rol oynar. Ek olarak, merkezi opioiderjik sistemler beslenme davranışının düzenlenmesinde rol oynar. Nöropeptitler hipotalamusta eksprese edilen moleküllerdir ve gıda alımının düzenlenmesine de katkıda bulunurlar. Bu çalışmanın amacı, mu opioiderjik agonist/antagonist moleküllerin hipotalamusta hem oreksijenik hem de anoreksijenik peptitler üzerindeki etkilerini araştırmaktır.
Yöntemler: Çalışmamızda 48 erkek Wistar albino sıçan kontrol, morfin, nalokson ve morfin+nalokson olmak üzere 4 gruba ayrıldı. Kontrol grubuna 5 gün boyunca subkutan SF solüsyonu; morfin grubuna 5 gün boyunca 10 mg/kg/gün dozunda morfin; nalokson grubuna 5 gün boyunca SF ve son enjeksiyondan 1,5 saat sonra 3 mg/kg dozunda nalokson; morfin+nalokson grubuna 5 gün boyunca morfin enjeksiyonundan 1,5 saat sonra nalokson uygulandı. Deneklerin başları kesilmiş ve hipotalamus dokuları nazikçe çıkarılmıştır. Anoreksijenik ve oreksijenik peptid ekspresyon düzeyleri RT-PCR yöntemi ile analiz edildi.
Sonuçlar: Morfin uygulaması OX2R ve LepR genlerinin ekspresyon seviyelerinde azalmaya neden olurken, ORXA, OX1R, AgRP, NPY, POMC gen ekspresyonunu önemli ölçüde değiştirmedi. Nalokson uygulaması AgRP ve NPY ekspresyonunu artırırken OX2R, LepR ve APLNR gen ekspresyon düzeylerini azaltmıştır.
Sonuçlar: Bu bulgular morfinin hipotalamusta beslenme ve metabolizma ile ilgili moleküllerin gen ekspresyonunu çeşitli düzeylerde etkileyebileceğini göstermektedir.

Keywords

Hipotalamus, sıçan, AgRP, apelin, NPY, POMC, nöropeptidler, NPY, morfin bağımlılığı

Ethical Statement

Bu proje Necmettin Erbakan Üniversitesi Deney Hayvanları Yerel Etik Kurulu tarafından onaylanmıştır (Proje Numarası: 2023-041)

Supporting Institution

Bu çalışma Necmettin Erbakan Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü tarafından 23YL18003 numaralı proje ile desteklenmiştir.

Project Number

23YL18003

Thanks

Necmettin Erbakan Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Ofisine desteklerinden dolayı teşekkür ederiz.

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