Sıçanlarda Bupropion ve Vareniklinin Morfin Yoksunluğu Sendromu Üzerine Etkileri

Abstract

Amaç: Opioid bağımlılığı, nüks ve remisyon ile karakterize kronik ve karmaşık bir hastalıktır. Kronik morfin uygulaması, fiziksel ve psikolojik bağımlılık semptomlarına neden olur. Bu çalışmanın amacı, bupropion ve vareniklin gibi anti-bağımlılık ilaçlarının morfin bağımlılığı ve nalokson ile hızlanırılmış yoksunluk sendromu üzerindeki etkisini sıçan modelinde araştırmaktı.
Gereç ve Yöntemler: Morfine bağlı fiziksel bağımlılığı değerlendirmek için, yetişkin erkek Wistar sıçanlarına 5 gün boyunca günde iki kez artan dozlarda morfin intraperitoneal (i.p.) uygulandı. 6. günde tek doz morfin uygulamasından 4 saat sonra yoksunluk semptomlarını ortaya çıkarmak için subkutan (s.c.) nalokson (2 mg/kg, s.c.) uygulaması yapıldı. Fiziksel bağımlılık, 15 dakika süreyle intraperitoneal (i.p.) bupropion (5, 10 ve 20 mg/kg, i.p.) ve vareniklin (0,5, 1 ve 2 mg/kg, s.c) verilerek değerlendirildi.
Bulgular: Morfin gurubunda kontrol grubuna göre önemli ölçüde yoksunluk semptomları görüldü. Sonuçlar, morfin bağımlılığının indüklenmesi sırasında bupropion ve vareniklin uygulamasının, yoksunluk semptomlarının şiddetinin çoğunu azalttığını gösterdi. Bupropionun birlikte uygulanması, sıçrama, ıslak köpek silkelenmesi, kilo kaybı ve toplam yoksunluk semptomlarını azaltmıştır. Vareniklinin birlikte uygulanmasının bupropion gibi yoksunluk semptomları üzerinde etkili olduğu, ancak kilo kaybı üzerinde etkisi olmadığı saptandı.
Sonuç: Bu sonuçlar, bupropion ve vareniklinin morfininin yoksunluk semptomlarını hafifletmek için aday ilaçlar olarak kullanılabileceğine dair ön veriler sağlamaktadır.

Keywords

• Morfin
• Bupropion
• Vareniklin
• Nalokson
• Opioid Yoksunluk Sendromu

The Effects of Bupropion and Varenicline on Morphine Withdrawal Syndrome in Rats

Abstract

Objective: Opioid dependence is a chronic complicated disorder characterized by relapse and remission. Chronic administration of morphine causes symptoms of physical and psychological dependence. The purpose of the present study was to investigate the effect of anti-addictive drugs such as bupropion and varenicline on morphine dependence and naloxone precipitated withdrawal syndrome in a rat model.
Materials and Methods: To assess the physical dependence of morphine, adult male Wistar rats were administered intraperitoneally (i.p.) increasing doses of morphine twice daily for 5 days, 4 hours after a single dose of morphine on day 6, and 15 minutes before subcutaneous (s.c.) naloxone (2 mg/kg, s.c.) administration to elicit withdrawal symptoms. Physical dependence was evaluated by injecting bupropion (5, 10, and 20 mg/kg, i.p.) and varenicline (0.5. 1, and 2 mg/kg, s.c.) for 15 minutes.
Results: The morphine-dependent rats more significantly demonstrated withdrawal symptoms than naive control rats. The results elucidated that administration of bupropion and varenicline during induction of morphine dependence attenuated the most of the severity of withdrawal symptoms. Co-administration of bupropion with morphine reduced withdrawal symptoms such as jumping, wet dog shaking, weight loss and total withdrawal symptoms. Co-administration of varenicline with morphine was found to be effective on withdrawal symptoms such as bupropion, but had no effect on weight loss.
Conclusion: These outcomes provide preliminary data which show that bupropion and varenicline can be used as a candidate drugs to attenuate morphine withdrawal symptoms.

Keywords

• Morfin
• Bupropion
• Vareniklin
• Nalokson
• Opioid Yoksunluk Sendromu

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