The effects of topiramate applied to the nucleus accumbens region on morphine withdrawal syndrome

Yıl 2020, , 240 - 248, 23.08.2020

Songül Özkula , Oya Helin Dundar Selcuk Erol Ramazan Bakar Heja Gecit N. Eymen Turan M. Fırat Balık Hasan Yananlı , Rezzan Gülhan , Mahluga Jafarova Demirkapu

https://doi.org/10.37696/nkmj.714162

Öz

Abstract:
Objective: Nucleus accumbens, one of the nuclei of the basal ganglia, and dopamine, the neurotransmitter play a critical role in opioid dependence and withdrawal. In opioid withdrawal, the importance of neurotransmitters such as glutamate and GABA, as well as dopamine, is known. In this study, we aimed to investigate the effects of local injections of topiramate, an antiepileptic agent affecting GABAergic and glutamatergic pathways, into the nucleus accumbens on withdrawal signs and locomotor activity during naloxone-induced withdrawal in morphine-dependent rats.
Material and Method: Twenty male Sprague-Dawley rats were divided in topiramete treatment and control groups. All animals received morphine pellets and guide cannulas were placed bilaterally in the nucleus accumbens regions by stereotaxic surgery. On the last day of the experiment, following the bilateral topiramate or saline (control group) microinjections, morphine withdrawal was triggered by naloxone.
Results: Topiramate microinjections into the nucleus accumbens region significantly suppressed the signs of naloxone-induced morphine withdrawal such as number of jumpings and weight loss. No significant difference was observed in wet dog shakes, one of the withdrawal signs, after local topiramate treatment. Although topiramate microinjections increased stereotypical activity it did not change locomotor activity behavior such as vertical and ambulatory activity, and total covered distance.
Conclusion: These findings show that local microinjection of topiramate into the nucleus accumbens is effective in preventing opioid deprivation symptoms without significant leffect on locomotor activity.

Anahtar Kelimeler

Morphine, topiramate, withdrawal, nucleus accumbens

Nukleus akumbens bölgesine uygulanan topiramatın morfin yoksunluk sendromu üzerine etkileri

Öz

Amaç: Bazal gangliyon çekirdeklerinden biri olan nukleus akumbens ve nörotransmitter olan dopamin opioid bağımlılığı ve yoksunluğunda kritik rol oynamaktadır. Opioid yoksunluğunda dopaminin yanı sıra glutamat ve GABA gibi nörotransmitterlerin de önemi bilinmektedir. Biz bu çalışmada morfin bağımlısı hayvanlarda GABAerjik ve glutamaterjik yolakları etkileyen antiepileptik ajan olan topiramatın nukleus akumbens bölgesine lokal uygulamasının naloksonla tetiklenen yoksunluk sendromunda yoksunluk bulguları ve lokomotor aktivite üzerine etkilerini araştırmayı amaçladık.
Materyal ve Metot: Yirmi adet erkek Sprague-Dawley sıçanları topiramat tedavi grubu ve kontrol grubuna ayrıldı. Hayvanların hepsine morfin peletleri uygulandı, stereotaksik cerrahi işlemle nukleus akumbens bölgelerine kılavuz kanüller bilaretal yerleştirildi. Deneyin son gününde bilateral topiramat veya serum fizyolojik (kontrol grubu) mikroenjeksiyonlarını takiben nalokson uygulanarak morfin yoksunluğu tetiklendi.
Bulgular: Nukleus akumbens bölgesine lokal uygulanan topiramat naloksonla tetiklenen morfin yoksunluk bulgularından sıçrama sayısını ve ağırlık kaybını anlamlı düzeyde baskıladı. Lokal topiramat uygulaması yoksunluk bulgularından ıslak köpek silkinmesinde ise anlamlı değişiklik yapmadı. Topiramat mikroenjeksiyonları stereotipik hareketleri artırdığı halde vertikal hareketler, ambulatuvar hareketler ve toplam kat edilen mesafe gibi lokomotor aktivite davranışlarını değiştirmedi.
Sonuç: Bu bulgular antikonvülzan ilaç olan topiramatın nukleus akumbens bölgesine lokal enjeksiyonunun opioid yoksunluğunda etkili olduğunu, lokomotor aktivitede anlamı baskılanma yapmadan santral etkilerin yanı sıra periferik etkiler oluşturduğunu göstermektedir.
Keywords: antikonvülzan; morfin; nukleus akumbens; sıçrama; ağırlık kaybı; lokomotor aktivite

Anahtar Kelimeler

Morfin, nükleus akümbens, morfin, yoksunluk

Kaynakça

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