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  • Ergoline derivative LEK-8829-inducet turning behavior in rats with unilateral striatal ibotenic acid lesions : interaction with bromocriptine
    Šprah, Lilijana ; Živin, Marko, 1958- ; Sket, Dušan
    LEK-8829 (9, 10-didehydro-N-methyl-(2-propynyl)-6-methyl-8-aminomethylergolinebimaleinate) is an antagonist of dopamine D2 receptors and serotonin (5-HT)2 and 5-HT1A receptors in infact animals and a ... D1 receptor agonist in dopamine-depleted animals. In the present study, we used rats with unilated striatal lesions with ibotenic acid (IA) to investigate the dopamine receptor activities of LEK-8829 in a model with innervated dopamine receptors. The IA-lesioned rats circled ipsilaterally when challenged with apomorphine, the mixed agonist on D1/D2 receptors. LEK-8829 induced a dose-dependent contralateral turning that was blocked by D, receptor antagonist SCH-23390. The treatment with D1 receptor agonist SKF-825958 induced ipsilateral turning, whereas the treatmentwith D2 receptor antagonist haloperidol induced contralateral posture. The combined treatment with SKF-82958 and haloperidol resulted in a weak contralateral turning, indicating the possible receptor mechanism of contralateral turning induced by LEK-8829. Bromocriptine induced a weak ipsilateral turning that was blocked by haloperidol. The ipsilateral turning induced by bromocriptine was significantly potentiated by the coadministrationof a low dose but not by a high dose of LEK-8829. The potentiation of turning was blocked either by SCH-23390 or by haloperidol. Thepotentiation of ipsilateral turning suggests the constimulation of D2 and D1 receptors by bromocriptine and LEK-8829, respectively, whereas the lack of potentiation by the highest dose of LEK-8829 may be explained by the opposing activity of LEK-8829 and bromocriptine at D2 receptors. We propose that the D2and 5HT2 receptor-blocking and D1 receptor-stimulating profile of LEK-8829 is promising for the treatment of negative symptoms of schizophrenia.
    Vir: The Journal of pharmacology and experimental therapeutics. - ISSN 0022-3565 (Letn. 288, št. 3, 1999, str. 1093-1100)
    Vrsta gradiva - članek, sestavni del
    Leto - 1999
    Jezik - angleški
    COBISS.SI-ID - 9865945

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