Author/Editor     Šprah, Lilijana
Title     Učinek spojine LEK-8829 na dopaminskih receptorjih pri podgani z enostransko okvaro striatuma
Type     monografija
Place     Ljubljana
Publisher     Medicinska fakulteta
Publication year     1999
Volume     str. 151
Language     slo
Abstract     Previous experiments have suggested a potential atypical antipsychotic activity of the ergoline derivative LEK-8829 (9,10-didehydro-N-methyl-(2-propynyl)-6-methyl-8-aminomethylergoline bimaleinate). Experiments in vitro showed a high affinity to 5-HT1A, 5-HT2 and D-2 receptors and a moderate affinity to D-1 receptors. The ratio of pKi values 5-HT2/D-2 was similar to the ratio of atypicat antipsychotic clozapine. In vivo experiments showed an antagonism of dopamine and serotonin receptor-linked behaviors of LEK-8829. By using animal models with supersensitive dopamine receptors it was also found that LEK-8829 is an antagonist of dopamine D-2 receptors and an agonist of dopsmine D-1 receptors in dopamine depleted striatum. The aim of thesis was to study the effects of LEK-8829 on movement and on gene expression within striatum in order to determine its effects on dopaminergic transmission. It was hypothesized that LEK-8829 simultaneously stimulates and blocks dopsminergic transmission via dopamine D-1 and D-2 receptors, respectively. Rats with unilateral striatat lesions with ibotenic acid (IA) represent an animal model with normosensitive dopamine receptors that is appropriate for the studies of the effects of dopaminergic drugs on locomotor activity. In this model, IA destroys dopaminoceptive striatal efferent neurons. The locomotor etfects of dopaminergie drugs are therefore thought to bo conveyed by the normosensitive dopamine receptors of the intact side. For example, turning toward the lesioned side (ipsilateral turning) is induced when dopamine D-1 and D-2 receptors on the intact side are directly or indirectly eostimulated by apomorphine or by amphetamine. The IA-lesioned rats displayed intensive ipsilateral turning when challenged with either apomorphine or amphetamine. (Abstract truncated at 2000 characters.)
Descriptors     CORPUS STRIATUM
RECEPTORS, DOPAMINE
BEHAVIOR, ANIMAL
ERGOLINES
RATS
RECEPTORS, DOPAMINE D1
RECEPTORS, DOPAMINE D2
APOMORPHINE
AMPHETAMINE
HALOPERIDOL
CLOZAPINE
ACETYLCHOLINESTERASE
CYTOCHROME-C OXIDASE
GENE EXPRESSION
IN SITU HYBRIDIZATION
HISTOCYTOCHEMISTRY
MOVEMENT DISORDERS
NEUROTENSIN
TACHYKININS
RNA, MESSENGER
ENKEPHALINS