Investigating the role of imidazoline-2 receptors in in vivo model of morphine dependence

Year 2011, Volume: 1 Issue: 2, 88 - 95, 31.01.2014

Zehra Çetin Tijen Utkan Alan Hudson Feyza Arıcıoğlu

Abstract

Objective: The present study was designed to investigate the effects of imidazoline (I) receptors, especially I2 subtype, in in vivo morphine dependence.
Methods: In vivo study was done by observing behavioural signs of morphine withdrawal in morphine dependent rats after treatment with selective I2 receptor agonist 2-BFI and selective I2 receptor antagonist BU224. Two morphine pellets, each containing 75 mg of morphine base, were implanted subcutaneously in the scapular area of Sprague-Dawley rats. Seventy-two hours after morphine implantation, 2-BFI (3, 5, 10 mg/kg), BU224 (3, 5, 10 mg/kg) or saline was injected to rats intraperitoneally (i.p.). Thirty minutes later, a morphine withdrawal syndrome was precipitated by naloxone (2 mg/kg). Just after the naloxone injection, morphine withdrawal signs such as jumping, wet dog shakes, teeth chattering, defecation, diarrhea, tremor and ptosis were observed and evaluated for 15 min.
Results: Both 2-BFI and BU224, which are administered before naloxone-precipitated withdrawal syndrome, attenuated withdrawal symptoms dose dependently. Low doses of 2-BFI (3 mg/kg) on jumping and low dose of BU224 were found ineffective on wet dog shakes and weight lost.
Conclusion: The present study showed that both 2-BFI and BU224 attenuated the intensity of many signs of the naloxoneprecipitated morphine withdrawal syndrome in rats. Based on these findings, it is thought that imidazoline system may play an important role in morphine dependence and morphine withdrawal, via it’s receptors or/and other mechanisms.

Key words: 2-BFI, BU224, imidazoline-2 receptors, dependence, morphine

Keywords

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İmidazolin-2 reseptörlerinin rolünün in vivo morfin bağımlılığı modelinde araştırılması

Abstract

Amaç: Bu çalışma son yıllarda tanımlanan imidazolin (I) reseptörlerinin özellikle I2 alt tipine seçici olarak bağlanan maddelerden yararlanarak söz konusu reseptörlerin morfin bağımlılığındaki etkisini araştırmak üzere planlanmıştır.
Yöntem: I2 reseptörlerinin agonisti olan 2-BFI ve antagonisti olan BU224 in vivo bağımlılık modellerinde kullanılmıştır. İn vivo bağımlılık Sprague-Dawley sıçanlara ciltaltı morfin peleti (toplam 150 mg) yerleştirilerek oluşturulmuştur. İmplantasyondan 72 saat sonra intraperitoneal (i.p.) olarak 2-BFI (3, 5 veya 10 mg/ kg) veya BU224 (3, 5 veya 10 mg/kg) uygulamasından 30 dakika sonra nalokson (2 mg/kg) enjekte edilerek değerlendirilmiştir. Nalokson uygulamasının hemen ardından sıçanlar 15 dakika boyunca gözlenerek sıçrama, ıslak köpek titremesi, karın germe, defekasyon, pitozis, diş gıcırdatma, diyare, tremor gibi morfin yoksunluğu belirtileri kaydedilmiştir.
Bulgular: Hem 2-BFI hem de BU224 naloksonla yoksunluk sendromu oluşturmadan önce uygulandığında yoksunluk semptomlarını doza bağımlı bir biçimde baskılanmıştır. 2-BFI’nın en düşük dozu (3 mg/kg) sıçramada ve BU224’ün en düşük dozu (3 mg/kg) ıslak köpek titremesi ve kilo kaybında etkisiz bulunmuştur.
Sonuç: Hem 2-BFI hem de BU224’ün yoksunluk semptomlarını baskıladığı gösterilmiştir. Bu çalışmanın sonuçları I sisteminin belki kısmen reseptörleri aracılığıyla belki de farklı mekanizmaları kullanarak morfin bağımlılığı ve/veya yoksunluğunda önemli rolü olduğunu düşündürmektedir.

Anahtar Kelimeler : 2-BFI, BU224, imidazolin-2 reseptörleri,bağımlılık, morfin

Keywords

2-BFI, BU224, imidazolin-2 reseptörleri, bağımlılık, morfin

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