Sıçanda Ventral ve Dorsal Striatumun Hafif ve Ağır Dopaminerjik Denervasyonu Modellerinde Apomorfinle Tetiklenecek Dopamin Disregülasyon Sendromu ve Dürtü Kontrol Bozukluğunun İncelenmesi

Abstract

ÖZKAN E., İnvestigation of dopamin dysregulation syndrome and impulse control disorders induced by apomorphine in rat partial and total dopaminergic denervation model at ventral and dorsal striatum. Hacettepe University Faculty of Medicine, Thesis in Neurology. Ankara, 2016. In Parkinson’s disease, dopamine replacement therapy related impulse control disorders and dopamine dysregulation syndrome are associated with reduced quality of life. Few studies demonstrated that this behaviours stem from a DA-dependent sensitization to appetitive stimuli within the ventral striatum. In this study, we aimed to build an animal model of this behaviours, extend the knowledge about pathophysiology of this behaviours and investigate the role of ventral/dorsal distribution of dopaminergic denervation. For this purposes, we developed experimental model of parkinsonism by injection of 6-hydroxydopamine toxin to bilateral VTA or SN. For exploring the rewarding properties of low dose apomorphine, the preference of drug paired compartment after conditioning of these rat is studied at conditioned place preference paradigm. After CPP experiment, these rats are treated with daily high dose apomorfine. Drug induced stereotypic and dyskinetic behaviours analysed with suitable scales. Study also included rats with parkinsonism treated with saline and normal rats treated with saline or apomorphine. At the end of all behavioural tests, extend of dopaminergic denervation is showed with tyrosine hydroxylase immunohistochemistry staining. The rats which was made dopaminergic denervation and treated with apomorphine developed dyskinetic behaviours. The severity of this behaviours increased day by day and they were strongly and positively correlated with mean lesion volume. Low dose apomorfine induced CPP at rats with parkinsonism and CPA at normal rats. The conditioning score was moderately and positively correlated with mean ventral lesion volume. The stereotypic behaviours was attenuated at rats with dorsal predominated dopaminergic loss. Further studies are needed to find out moleculer mechanisms of this findings.