Santral sinir sistemine akut uygulanan topiramatin morfin yoksunluk sendromuna ve beyin kaynakli nörotrofik faktöre etkisi

Objectives: Nucleus accumbens(NAc) is known to have a role in the addiction caused by the use of opioids. Topiramate is a new generation antiepileptic drug that increases postsynaptic gamma-aminobutyric acid receptor activity and antagonizes glutamatergic receptors. Brain-derived neurotrophic factor(BDNF) that play a role in synaptic plasticity, and proBDNF in apoptosis. In this study, the effect of topiramate on naloxone-induced morphine abstinence syndrome and the effects on the levels of BDNF/proBDNF were investigated. Materials and Methods: In this study 38 Wistar rats were implanted stereotaxically with cannulas bilaterally into lateral ventricle(ICV) or NAc region. After stereotaxic surgery three pellets containing 75 mg of base morphine were implanted subcutanously. Topiramate(100 µM/site) was administered ICV(2µL) or into the NAc(500nL), and the abstinence has been triggered by naloxone(3mg/kg, i.p.). At the end of the experiments brains were removed and the frontal cortex were isolated and the BDNF/proBDNF levels were examined using the Western Blot method. Results: In the morphine abstinence triggered by naloxone, the ICV or NAc administration of topiramate has significantly suppressed the number of jumps. Topiramate administered to NAc, has significantly decreased stereotypical behavior, while no change in the locomotor activity were observed. Topiramate administered ICV, significantly reduced BDNF/proBDNF ratio, whereas topiramate administered to NAc significantly increased BDNF/proBDNF ratio. Conclusion: These findings showed that topiramate administered ICV and into the NAc reduced naloxone-induced morphine abstinence symptoms and stereotypic locomotor activity and changed the ratio of BDNF/proBDNF, which plays a role in synaptic plasticity/apoptosis. Key Words: Morphine, nucleus accumbens, topiramate, BDNF, proBDNF