Deneysel Morfin Bağımlılığı Modeli Oluşturulmuş Sıçanlarda Hipokampus ve Hipotalamustaki Melatonin Reseptörleri Gen İfade Düzeylerinin Araştırılması
Yükleniyor...
Dosyalar
Tarih
2020
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Necmettin Erbakan Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Melatonin, iki farklı G proteinine bağlı membran reseptörü olan MT1 ve MT2 aracılığıyla
birçok fizyolojik etkisini gösterir. Ek olarak, son çalışmalar bu reseptörlerin MT1/MT2 heteromer
oluşumunu ortaya koymaktadır. Bu çalışmanın amacı, sıçan hipokampusu ve hipotalamusta morfin
bağımlılığı ve morfin yoksunluğu durumunda bu melatonin reseptörlerinin gen ekspresyon düzeylerini
araştırmaktır.
Bu çalışmada 300-350 gr ağırlığında 36 adet Wistar ırkı erkek sıçanlar kullanıldı. Hayvanlar
12’şerli olarak 3 gruba ayrıldı. Kontrol grubuna serum fizyolojik, morfin ve morfin + nalokson
gruplarına 10 mg/kg/gün morfin sülfat 6 gün boyunca deri altı yolla uygulandı. 7. gün kontrol ve morfin
gruplarına serum fizyolojik, morfin + nalokson grununa ise 1 mg/kg nalokson periton içi yolla enjekte
edildi ve 30 dakika süreyle davranış parametreleri belirlendi. Tüm sıçanların hipokampus ve
hipotalamus dokularındaki melatonin reseptörleri gen ekspresyon seviyeleri kantitatif RT-PCR ile
analiz edildi. İstatistiksel değerlendirmelerde yönlü ANOVA kullanıldı.
Deney hayvanlarına nalokson uygulanması sonucunda hayvanlarda belirgin şekilde morfin
çekilme davranış bulguları saptandı. Hipokampus dokusunda melatonin reseptörlerinin gen ifadesi
seviyelerinde gruplar arasında anlamlı bir fark yoktu. Hipotalamusta MT1 reseptör gen ifadesi, kontrol
grubuna göre bağımlılık ve nalokson grubunda anlamlı olarak yüksek bulundu (p <0.05). Benzer
şekilde, bağımlılık ve nalokson grubunda kontrol grubuna göre MT1/MT2 heteromer reseptör
ifadesinde artmış artmış olarak dedekte edildi (p <0.05). Hipotalamustaki MT2 reseptör ifade seviyeleri
arasında anlamlı bir fark yoktu.
Morfin çekilme grubu bulguları göz önüne alındığında, bir haftalık morfin uygulanmasıyla
sıçanlarda belirgin olarak bağımlılık oluştuğu gözlenmiştir. Hipotalamusta melatonin gen ifade
seviyelerinin artması, morfin bağımlılığında hipotalamusun melatoninerjik etkiye daha duyarlı hale
gelebileceğini düşündürmektedir.
Melatonin exerts many physiological effects via two different G protein-coupled membrane receptors, MT1 and MT2. Additionally, recent studies also reveal MT1/MT2 heteromer formation of these receptors. The aim of this study was to investigate gene expression levels of these melatonin receptors in morphine dependence and morphine withdrawal condition in rat hippocampus and hypothalamus. In this study, 36 male Wistar rats weighing 300-350 g were used. The animals were divided into 3 groups of 12. In the control group, saline, morphine and morphine + naloxone groups were administered subcutaneously 10 mg/kg/day morphine sulfate for 6 days. On the 7th day, saline was injected intraperitoneally to the control and morphine groups, and 1 mg / kg naloxone to the morphine + naloxone group intraperitoneally and behavioral parameters were determined for 30 minutes. Melatonin receptors gene expression levels in hippocampus and hypothalamus tissues of all rats were analyzed by quantitative RT-PCR. Directional ANOVA was used for statistical evaluations. As a result of naloxone administration to experimental animals, significant morphine withdrawal behavior findings were detected in animals. There was no significant difference between the groups in gene expression levels of melatonin receptors in the hippocampus tissue. MT1 receptor gene expression in the hypothalamus was significantly higher in the addiction and naloxone groups compared to the control group (p<0.05). Similarly, an increased MT1/MT2 heteromer receptor expression was detected in the addiction and naloxone group compared to the control group (p <0.05). There was no significant difference between MT2 receptor expression levels in the hypothalamus. Considering the morphine withdrawal group findings, a significant dependence was observed in rats after administration of morphine for one week. Increased melatonin gene expression levels in the hypothalamus suggest that the hypothalamus may become more sensitive to melatoninergic effect in morphine addiction.
Melatonin exerts many physiological effects via two different G protein-coupled membrane receptors, MT1 and MT2. Additionally, recent studies also reveal MT1/MT2 heteromer formation of these receptors. The aim of this study was to investigate gene expression levels of these melatonin receptors in morphine dependence and morphine withdrawal condition in rat hippocampus and hypothalamus. In this study, 36 male Wistar rats weighing 300-350 g were used. The animals were divided into 3 groups of 12. In the control group, saline, morphine and morphine + naloxone groups were administered subcutaneously 10 mg/kg/day morphine sulfate for 6 days. On the 7th day, saline was injected intraperitoneally to the control and morphine groups, and 1 mg / kg naloxone to the morphine + naloxone group intraperitoneally and behavioral parameters were determined for 30 minutes. Melatonin receptors gene expression levels in hippocampus and hypothalamus tissues of all rats were analyzed by quantitative RT-PCR. Directional ANOVA was used for statistical evaluations. As a result of naloxone administration to experimental animals, significant morphine withdrawal behavior findings were detected in animals. There was no significant difference between the groups in gene expression levels of melatonin receptors in the hippocampus tissue. MT1 receptor gene expression in the hypothalamus was significantly higher in the addiction and naloxone groups compared to the control group (p<0.05). Similarly, an increased MT1/MT2 heteromer receptor expression was detected in the addiction and naloxone group compared to the control group (p <0.05). There was no significant difference between MT2 receptor expression levels in the hypothalamus. Considering the morphine withdrawal group findings, a significant dependence was observed in rats after administration of morphine for one week. Increased melatonin gene expression levels in the hypothalamus suggest that the hypothalamus may become more sensitive to melatoninergic effect in morphine addiction.
Açıklama
Yüksek Lisans Tezi
Anahtar Kelimeler
Hipokampus, hipotalamus, melatonin reseptörleri, morfin bağımlılığı, nalokson, Hippocampus, hypothalamus, melatonin receptors, morphine dependency, naloxone
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Çimen, Y. A. (2020). Deneysel morfin bağımlılığı modeli oluşturulmuş sıçanlarda hipokampus ve hipotalamustaki melatonin reseptörleri gen ifade düzeylerinin araştırılması. (Yayınlanmamış Yüksek Lisans Tezi). Necmettin Erbakan Üniversitesi Sağlık Bilimleri Enstitüsü Fizyoloji Anabilim Dalı, Konya
