Nukleus Akumbens Bölgesine Uygulanan Topiramatın Morfin Yoksunluk Sendromuna Etkileri

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.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 opioid dependence 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, 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.Materials and Methods:Twenty male Sprague-Dawley rats were divided in topiramate 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 effect on locomotor activity

Santral sinir sistemine akut uygulanan topiramatın morfin yoksunluk sendromuna ve beyin kaynaklı nörotrofik faktöre etkisi

Santral Sinir Sistemine Akut Uygulanan Topiramatın Morfin Yoksunluk Sendromuna ve Beyin Kaynaklı Nörotrofik Faktöre Etkisi--------------------The Effect of Acute Topiramate Administration on Morphine Withdrawal Syndrome and Brain-derived Neurotrophic Factor in Central Nervous Syste

In vitro contractile responses of human detrusor smooth muscle to oxytocin: does it really have effect?

Background and objectives: The aim of this study was to investigate the contractile effects of oxytocin (OT) in human detrusor muscle in in vitro conditions. Material and Methods: Human detrusor muscle samples were obtained from seven patients that undergone radical cystectomy. Four female Wistar rats' uterine samples were used as control. Contractile responses were tested of carbachol in organ bath. Cumulative concentration response curves were constructed to OT and then the strips were incubated with atosiban (OT antagonist) and a second concentration response curve to OT were constructed. Results: Carbachol, contracted all human strips for the functionality test whereas OT in any concentrations did not produce significant contraction on all human strips. In only one bladder strip and in a very high concentration slight contraction was recorded. Moreover no contractile response was recorded in any OT concentrations in the presence of atosiban. The rat uterine strips responded to OT in a dose dependent manner. Atosiban, the OT receptor antagonist diminished totally those contractile responses. Conclusion: It is been demonstrated here that there is no contractile response to OT in human detrusor muscle. These findings should be supported by further investigations determining the presence of the OT receptor in human detrusor