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Kappa Opioid Reseptörlerin Sıçan Hipokampus, Hipotalamus Ve Striatum Bölgelerinde Serotonerjik Nörotransmisyonu Modülasyonu

Kappa Opioid Modulation of Serotonergic Neurotransmission in the Hypothalamus, Hippocampus and Striatum in the Male Rat

Journal Name:

  • Fırat Tıp Dergisi

Publication Year:

  • 2006

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Abstract (2. Language): 
Objectives: We have investigated the modulatory effects of K-opioid receptors on the central serotonergic system in the hypothalamus, hippocampus and striatum. Materials and Methods: Male Sprague-Dawley rats (n=32) used in the experiments were divided into four groups. Anaesthetized animals were mounted on a stereotaxic apparatus and intracerebroventricularly infused with U-50488H (K-agonist, 50|lg/kg), Nor-BIN (K-antagonist, 50|lg/kg) or U-50488H + Nor-BIN. Control group received saline alone. A l l animals were decapitated 30 mins after infusions. Hypothalamus, hippocampus and striatum were microdissected and snap frozen. Concentrations of 5-hydroxytryptamin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA, 5-HT metabolite) in these brain regions were determined by HPLC-ECD. Results: 5-HT and 5-HIAA values in the hypothalamus and hippocampus of U-50488H-treated group were significantly decreased compared to control group (p<0.01 and p<0.05). Indoleamine levels (ng/gr tissue) in the K-antagonist group were found to be similar to or slightly lower than the control values (p<0.05). Nor-BIN reversed the U-50488H inhibition of 5-HT release in the agonist+antagonist treated group (p<0.001). 5-HT levels in the striatum of all three groups were significantly higher than control group (p<0.01), 5-HIAA concentrations in the same brain region significantly decreased (p<0.001). Ratio of 5-HIAA/5-HT in the hypothalamus, hippocampus and striatum was significantly (p<0.05 and p<0.001, respectively) lowered by the K-agonist. Conclusion: These results suggest that K-opioid receptors modulate serotonergic neurotransmission in the hypothalamus, hippocampus and striatum. ©2006, Fırat Üniversitesi, Tıp Fakültesi
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Abstract (Original Language): 
Amaç: Bu çalışma, kappa opioid reseptörlerinin hipotalamus, hipokampus ve striatum'da serotonerjik nörotransmisyon üzerine modülatör etkilerinin araştırılması amacıyla yapıldı. Gereç ve Yöntem: Deneylerde kullanılan toplam 32 erkek Sprague-Dawley sıçan dört gruba ayrıldı. Anestezi altına alınan sıçanlar stereotaksik cihaza yerleştirildikten sonra, U-50488H (kappa agonist, 50|xg/kg), Nor-Binaltorphimine (Nor-BIN, kappa antagonist, 50|xg/kg) veya U-50488H + Nor-BIN intraserebroventriküler (ICV) yolla infüze edildi. Kontrol grubunu oluşturan hayvanlara ise aynı yolla serum fizyolojik uygulandı. ICV infüzyonlardan 30 dk sonra tüm sıçanlar dekapite edilerek beyinleri hızla kuru buz üzerine alındı. Mikrodiseksiyon yöntemiyle hipokampus, hipotalamus ve striatum bölgeleri çıkartılarak sıvı nitrojende donduruldu. Bu beyin bölgelerindeki 5-hydroxytryptamin (5-HT) ve 5-hydroxyindole acetic acid (5-HIAA, 5-HT metaboliti) düzeyleri HPLC-ECD yöntemiyle belirlendi. Bulgular: 5-HT ve 5-HIAA değerleri (ng/gr doku) U-50488H grubu hipotalamus ve hipokampus bölgelerinde kontrol grubuna göre anlamlı derecede azaldı (p<0.01 ve p<0.05). Kappa opioid antagonistinin tek başına verildiği grupta indolamin düzeylerinin kontrol grubu değerlerine yakın veya azalmış olduğu gözlendi (p<0.05). İki opioid ajanın kombine olarak uygulandığı grupta ise Nor-BIN'in, kappa agonistinin sebep olduğu serotonerjik inhibisyonu anlamlı derecede geri çevirdiği belirlendi (p<0.001). Striatumda elde edilen 5-HT düzeyleri her üç grupta da kontrol grubuna göre anlamlı olarak artmışken (p<0.01), aynı beyin bölgesinde belirlenen 5-HT metabolit (5-HIAA) değerleri ise oldukça anlamlı derecede azaldı (p<0.001). Sonuç: Bu bulgular, kappa opioid reseptörlerinin hipotalamus, hipokampus ve striatum bölgelerinde serotonerjik nörotransmisyonu modüle ettiklerini göstermektedir. ©2006, Fırat Üniversitesi, Tıp Fakültesi
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