Naslov
Ergoline derivate LEK-8829-induced turning behavior in rats with unilateral striatal ibotenic acid lesions: interaction with bromocriptine

Autori
Šprah, Ljiljana ; Živin, Marko ; Sket, Dušan

Izvornik
Journal of Pharmacology and Experimental Therapeutics (0022-3565) 288 (1999), 3; 1093-1100

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
ergoline derivate; turning behavior; ibotenic acid; bromocriptine

Sažetak
LEK-8829 [9, 10-didehydro-N-methyl-(2-propynyl)-6-methyl-8-aminomethylergoline bimaleinate] is an antagonist of dopamine D-2 receptors and serotonin (5-HT)(2) and 5-HT1A receptors in intact animals and a D-1 receptor agonist in dopamine-depleted animals, In the present study, we used rats with unilateral 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 D-1/D-2 receptors. LEK-8829 induced a dose-dependent contralateral turning that was blocked by D-1 receptor antagonist SCH-23390. The treatment with D-1 receptor agonist SKF-82958 induced ipsilateral turning, whereas the treatment with D-1 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 coadministration of 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. The potentiation of ipsilateral turning suggests the costimulation of D-2 and D-1 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 D-2 receptors. We propose that the D-2 and 5HT(2) receptor-blocking and D-1 receptor-stimulating profile of LEK-8829 is promising for the treatment of negative symptoms of schizophrenia.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA