Mahluga JAFAROVA DEMİRKAPU, Hasan Raci YANANLI, Songül ÖZKULA, Rezzan GÜLHAN, Oya Helin DUNDAR, Selçuk EROL, Ramazan BAKAR, Heja GECİT, N. Eymen TURAN, M. Fırat BALIK

Nukleus Akumbens Bölgesine Uygulanan Topiramatın Morfin Yoksunluk Sendromuna Etkileri

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 bağımlılığı oluşturulan 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 grubu olarak ikiye 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 uygulanmasının lokomotor aktivitede anlamlı baskılanma yapmadan opioid yoksunluk belirtilerinin önlenmesinde etkili olduğunu göstermektedir.

THE EFFECTS OF TOPIRAMATE APPLIED TO THE NUCLEUS ACCUMBENS REGION ON MORPHINE WITHDRAWAL SYNDROME

Aim: Nucleus accumbens, one of the nuclei of the basal ganglia, and dopamine, the neurotransmitter play a critical role in opioiddependence and withdrawal. In opioid withdrawal, the importance of neurotransmitters such as glutamate and gamma aminobutyric acid(GABA), as well as dopamine, is known. In this study, we aimed to investigate the effects of local injections of topiramate, anantiepileptic agent affecting GABAergic and glutamatergic pathways, into the nucleus accumbens on withdrawal signs and locomotoractivity during naloxone-induced withdrawal in morphine-dependent rats.Materials and Methods: Twenty male Sprague-Dawley rats were divided in topiramate treatment and control groups. All animalsreceived morphine pellets and guide cannulas were placed bilaterally in the nucleus accumbens regions by stereotaxic surgery. On thelast day of the experiment, following the bilateral topiramate or saline (control group) microinjections, morphine withdrawal was triggeredby naloxone.Results: Topiramate microinjections into the nucleus accumbens region significantly suppressed the signs of naloxone-inducedmorphine withdrawal such as number of jumpings and weight loss. No significant difference was observed in wet dog shakes, one of thewithdrawal signs, after local topiramate treatment. Although topiramate microinjections increased stereotypical activity it did not changelocomotor 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 opioiddeprivation symptoms without significant effect on locomotor activity.

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