Nucleus Accumbens'te Morfine Bağlı Dopamin Salınımının Fiber Fotometri ile Araştırılması

Yasin Ali Çimen, Selim Kutlu

  • Year : 2025
  • Vol : 41
  • Issue : 4
  •  Page : 194-200
Amaç: Morfin, akut ve kronik ağrı tedavisinde sıklıkla kullanılan bir opiyattır. Nucleus accumbens (NAc) ödül yolunun en temel merkezidir. Bağımlılık gelişimi ve ödül yolağının aktif olması bölgedeki dopaminerjik aktivitenin değişimi ile ilişkilendirilmiştir. Ardışık morfin kullanımı ventral tegmental alandaki dopaminerjik nöronların aktivasyonu yoluyla nükleus akumbenste dopamin düzeylerini artırır. Son zamanlarda popüler olmaya başlayan fiber fotometri sistemiyle dopaminerjik sensörlerden hızlı, anlık, tekrarlanabilir ve in vivo dopaminerjik sinyal kaydı yapılmaktadır. Konuyla alakalı çeşitli çalışmalar olmasına rağmen mevcut çalışmalar sınırlıdır. Çalışmanın amacı, yüksek teknolojili fiber optik fotometri sistemi kullanarak morfin bağımlılığı ve yoksunluğu sırasında NAc'deki dopaminerjik sinyalleri dopaminerjik sensör (GRABDA) vasıtasıyla araştırmaktır.
Gereç ve Yöntemler: Erkek Wistar sıçanlar morfin (M) ve morfin+nalokson (M+N) olmak üzere iki gruba ayrılmıştır. Fiber fotometri kaydı için tüm hayvanların sağ NAc bölgesine GRABDA enjekte edilmiştir. GRABDA, yapısında dopamin reseptörü 2’ye (DRD2) dayalı bir tanıma alanı içerir. Bu alana dopamin bağlandığında sensördeki yeşil floresan protein aktive olur. Oluşan floresan değişim, bölgedeki dopaminerjik aktiviteyi ve sinyal iletimini yansıtır. Daha sonra aynı bölgeye bir fiber optik kablo diş çimentosu ile sabitlenmiştir. 15 günlük dinlendirmenin ardından, 5 gün boyunca 10mg/kg morfin intraperitoneal olarak enjekte edilmiştir. Son enjeksiyondan sonra M+N grubuna 3mg/kg nalokson enjekte edilmiştir. Dopaminerjik sinyali ifade eden ortalama ΔF/F (%) değerleri, fiber fotometrik kayıtlar toplandıktan sonra Python ile hesaplanmıştır. ΔF/F (%) değeri, DRD2 reseptörlerine dopamin bağlanma düzeyini, normalize ederek yüzdelik olarak ifade eder. İstatistiksel karşılaştırmalar karma- ANOVA testi ve post-hoc karşılaştırmalar tahmini marjinal ortalamalar kullanılarak yapıldı.
Bulgular: M grubunun ΔF/F (%) değerleri morfin enjeksiyonu ile başlangıca kıyasla artmıştır (p<0.05). Nalokson enjeksiyonları sonucunda, M+N grubunun ΔF/F (%) değerleri M grubuna kıyasla önemli ölçüde azalmıştır (p<0.05). Morfin bağımlılığı NAc dopaminerjik sinyalini artırır. Nalokson bu artışı baskılar.
Sonuç: NAc'deki dopaminerjik aktivitenin yeni biyosensörlerle fiber fotometri ile saptanması, sıvı kromatografisi gibi eski tekniklerden daha etkili kanıt sağlama potansiyeline sahiptir. Konunun daha iyi anlaşılması için spesifik nöronal ve bölgesel çalışmalara ihtiyaç vardır.
Cite this Article As : Cimen YA, Kutlu S. Investigation of Morphine-Induced Dopamine Release in the Nucleus Accumbens by Fiber Photometry. Selcuk Med J 2025;41(4): 194-200

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Conflict of interest : The authors declare that they have no conflict of interest.
This article is published under the CC BY-NC 4.0 license.
Selcuk Medical Journal
2025, Vol. 41 (4)
ISSN: 1017-6616
E-ISSN: 2149-8059
Received : , Accepted : , Published Online :

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