The D1 receptor-mediated effects of the ergoline derivative LEK-8829 in rats with unilateral 6-hydroxydopamine lesions

British Journal of Pharmacology
Marko ZivinD Sket

Abstract

1. Previous experiments have suggested a potential atypical antipsychotic activity of the ergoline derivative LEK-8829. In vitro experiments showed a high affinity to 5-HT1A, 5-HT2 and D2 receptors (the ratio of pKi values 5-HT2/D2 = 1.11) and a moderate affinity to D1 receptors. In vivo experiments showed antagonism of dopamine and 5-hydroxytryptamine (5-HT) receptor-linked behaviours. 2. In the present study, the rats with unilateral dopaminergic deafferentation of the striatum, induced by the lesion of the median forebrain bundle with 6-hydroxydopamine (6-OHDA), were used to determine the effects of LEK-8829 on turning behaviour and on striatal c-fos mRNA levels. 3. The administration of LEK-8829 induced a long lasting contralateral turning behaviour that was dose-dependent. It was found that the specific D1 receptor antagonist SCH-23390 but not the D2 receptor antagonist haloperidol or 5-HT1A antagonist pindolol, dose-dependently inhibited the turning behaviour induced by LEK-8829. 4. In an attempt to clarify the D1:D2 receptor interactions involved in the action of LEK-8829 in the 6OHDA model, we used in situ hybridization histochemistry to compare the effect of SCH-23390 pretreatment on striatal c-fos mRNA expression indu...Continue Reading

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Citations

May 13, 2004·Naunyn-Schmiedeberg's Archives of Pharmacology·Natasa MilivojevicMarko Zivin
Jul 22, 1998·European Journal of Pharmacology·M ZivinD Sket
May 18, 2010·Neuroscience·N JelenM Zivin
Aug 28, 2007·Neuroscience Letters·Robert PalGordana Glavan
Nov 28, 2009·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Gordana GlavanMarko Zivin
Nov 20, 2018·Frontiers in Molecular Neuroscience·Anja PišlarJanko Kos
Dec 18, 2020·Frontiers in Molecular Neuroscience·Anja PišlarJanko Kos

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